Roles for Integrin α3β1 in Development and Disease

  • Chapter
  • First Online:
Integrins in Health and Disease

Part of the book series: Biology of Extracellular Matrix ((BEM,volume 13))

Abstract

Integrins are the major cell surface receptors for adhesion to the extracellular matrix, and their roles in normal physiology and disease pathologies have been the focus of intense investigation since they were discovered almost four decades ago. α3β1 is a laminin-binding integrin with particularly important roles in epithelial tissue development, homeostasis, and repair. The clinical importance of α3β1 is evident from patients that inherit mutations in the ITGA3 gene (which encodes the α3 integrin subunit), who are born with a multi-organ disorder that is often fatal within the first months of life and includes interstitial lung disease, nephrotic syndrome, and a mild form of epidermolysis bullosa. α3β1 also has important roles in wound healing and several types of cancer, including squamous cell carcinoma and breast cancer. In this chapter, we provide a comprehensive overview of α3β1 functions in normal physiology and how changes in these functions contribute to disease pathologies. Throughout our discussion, we highlight preclinical studies using cell culture models or genetically modified mice that have shed light on mechanisms through which α3β1 regulates a range of cell functions such as migration/invasion, proliferation, survival, matrix assembly/remodeling, and gene expression. We also discuss clinical and bioinformatic studies that support the relevance of these mechanisms to human health and disease. Much of our discussion centers on cutaneous wound healing as a paradigm for investigating roles for α3β1 in tissue remodeling. We then extend this discussion into the context of cancer, where α3β1 has either cancer-promoting or -suppressive roles depending on the cancer type/subtype or stage of progression. In both contexts, we emphasize an emerging role for α3β1 as a regulator of the keratinocyte secretome, allowing these cells to modify the tissue microenvironment through matrix remodeling or crosstalk to stromal cells during skin development, wound healing, or tumorigenesis. Finally, we discuss the prospect of exploiting α3β1 as a therapeutic target to treat cancer or pathological wounds, taking into consideration the associated challenges that arise from its complex biology.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (Canada)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (Canada)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (Canada)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AREs:

AU-rich elements

BM:

Basement membrane

BMP1:

Bone morphogenetic protein 1

Brain-2:

Brn-2/Oct-7/N-Oct3/POU3F2 transcription factor

CAFs:

Cancer-associated fibroblasts

CCN2:

Connective tissue growth factor

Cox-2:

Cyclooxygenase-2

CSF-1:

Colony-stimulating factor-1

DMBA:

7,12-Dimethylbenz[a]-anthracene

ECM:

Extracellular matrix

EMT:

Epithelial–mesenchymal transition

ERK:

Extracellular signal-regulated kinase

FAK:

Focal adhesion kinase

IAPs:

Integrin-associated proteins

ILNEB:

Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa

JEB:

Junctional epidermolysis bullosa

JNK:

c-Jun N-terminal kinase

LM:

Laminin

MAPKs:

Mitogen-activated protein kinases

MCP-1:

Macrophage chemoattractant protein 1

MMP:

Matrix metalloprotease

MRP-3:

Mitogen-regulated protein 3

MS:

Mass spectrometry

NMD:

Nonsense-mediated decay

OSCC:

Oral squamous cell carcinoma

RGD:

Arginine–glycine–aspartic acid motif present in many ECM ligands

RNAi:

RNA interference

SCC:

Squamous cell carcinoma

SMG:

Submandibular salivary gland

TAZ:

Transcriptional co-activator with a PDZ-binding domain

TEMs:

Tetraspanin-enriched microdomains

TGF-β:

Transforming growth factor β

TME:

Tumor microenvironment

TNBC:

Triple-negative breast cancer

TPA:

12-O-tetradecanoylphorbol-13-acetate

uPA:

Urinary-type plasminogen activator

uPAR:

Urokinase-type plasminogen activator receptor

VEGF:

Vascular endothelial growth factor

VLA:

Very late antigen

YAP:

Yes-associated protein

References

  • Abel EL, Angel JM, Kiguchi K, DiGiovanni J (2009) Multi-stage chemical carcinogenesis in mouse skin: fundamentals and applications. Nat Protoc 4:1350–1362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Amano S, Scott IC, Takahara K, Koch M, Champliaud MF, Gerecke DR, Keene DR, Hudson DL, Nishiyama T, Lee S, Greenspan DS, Burgeson RE (2000) Bone morphogenetic protein 1 is an extracellular processing enzyme of the laminin 5 gamma 2 chain. J Biol Chem 275:22728–22735

    Article  CAS  PubMed  Google Scholar 

  • Anton ES, Kreidberg JA, Rakic P (1999) Distinct functions of α3 and αv integrin receptors in neuronal migration and laminar organization of the cerebral cortex. Neuron 22:277–289

    Article  CAS  PubMed  Google Scholar 

  • Argraves WS, Suzuki S, Arai H, Thompson K, Pierschbacher MD, Ruoslahti E (1987) Amino acid sequence of the human fibronectin receptor. J Cell Biol 105:1183–1190

    Article  CAS  PubMed  Google Scholar 

  • Arias-Pinilla GA, Dalgleish AG, Mudan S, Bagwan I, Walker AJ, Modjtahedi H (2020) Development and application of two novel monoclonal antibodies against overexpressed CD26 and integrin alpha3 in human pancreatic cancer. Scientific Rep 10:537

    Article  CAS  Google Scholar 

  • Arosio D, Manzoni L, Corno C, Perego P (2017) Integrin-targeted peptide- and peptidomimetic-drug conjugates for the treatment of tumors. Recent Pat Anticancer Drug Discov 12:148–168

    Article  CAS  PubMed  Google Scholar 

  • Aumailley M (2013) The laminin family. Cell Adh Migr 7:48–55

    Article  PubMed  PubMed Central  Google Scholar 

  • Aumailley M (2021) Laminins and interaction partners in the architecture of the basement membrane at the dermal-epidermal junction. Exp Dermatol 30:17–24

    Article  CAS  PubMed  Google Scholar 

  • Aumailley M, Bruckner-Tuderman L, Carter WG, Deutzmann R, Edgar D, Ekblom P, Engel J, Engvall E, Hohenester E, Jones JC, Kleinman HK, Marinkovich MP, Martin GR, Mayer U, Meneguzzi G, Miner JH, Miyazaki K, Patarroyo M, Paulsson M, Quaranta V, Sanes JR, Sasaki T, Sekiguchi K, Sorokin LM, Talts JF, Tryggvason K, Uitto J, Virtanen I, von der Mark K, Wewer UM, Yamada Y, Yurchenco PD (2005) A simplified laminin nomenclature. Matrix Biol 24:326–332

    Article  CAS  PubMed  Google Scholar 

  • Aumailley M, El Khal A, Knoss N, Tunggal L (2003) Laminin 5 processing and its integration into the ECM. Matrix Biol 22:49–54

    Article  CAS  PubMed  Google Scholar 

  • Aumailley M, Pesch M, Tunggal L, Gaill F, Fassler R (2000) Altered synthesis of laminin 1 and absence of basement membrane component deposition in (beta)1 integrin-deficient embryoid bodies. J Cell Sci 113(Pt 2):259–268

    Article  CAS  PubMed  Google Scholar 

  • Avizienyte E, Frame MC (2005) Src and FAK signalling controls adhesion fate and the epithelial-to-mesenchymal transition. Curr Opin Cell Biol 17:542–547

    Article  CAS  PubMed  Google Scholar 

  • Avraamides CJ, Garmy-Susini B, Varner JA (2008) Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 8:604–617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baldwin G, Novitskaya V, Sadej R, Pochec E, Litynska A, Hartmann C, Williams J, Ashman L, Eble JA, Berditchevski F (2008) Tetraspanin CD151 regulates glycosylation of (alpha)3(beta)1 integrin. J Biol Chem 283:35445–35454

    Article  CAS  PubMed  Google Scholar 

  • Baleato RM, Guthrie PL, Gubler MC, Ashman LK, Roselli S (2008) Deletion of CD151 results in a strain-dependent glomerular disease due to severe alterations of the glomerular basement membrane. Am J Pathol 173:927–937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bellu E, Medici S, Coradduzza D, Cruciani S, Amler E, Maioli M (2021) Nanomaterials in skin regeneration and rejuvenation. Int J Mol Sci 22

    Google Scholar 

  • Berditchevski F (2001) Complexes of tetraspanins with integrins: more than meets the eye. J Cell Sci 114:4143–4151

    Article  CAS  PubMed  Google Scholar 

  • Berditchevski F, Gilbert E, Griffiths MR, Fitter S, Ashman L, Jenner SJ (2001) Analysis of the CD151-alpha3beta1 integrin and CD151-tetraspanin interactions by mutagenesis. J Biol Chem 276:41165–41174

    Article  CAS  PubMed  Google Scholar 

  • Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2:737–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bergmeier W, Hynes RO (2012) Extracellular matrix proteins in hemostasis and thrombosis. Cold Spring Harb Perspect Biol, p 4

    Google Scholar 

  • Bishop JL, Thaper D, Vahid S, Davies A, Ketola K, Kuruma H, Jama R, Nip KM, Angeles A, Johnson F, Wyatt AW, Fazli L, Gleave ME, Lin D, Rubin MA, Collins CC, Wang Y, Beltran H, Zoubeidi A (2017) The master neural transcription factor BRN2 is an androgen receptor-suppressed driver of neuroendocrine differentiation in prostate cancer. Cancer Discov 7:54–71

    Article  CAS  PubMed  Google Scholar 

  • Bonnans C, Chou J, Werb Z (2014) Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 15:786–801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boosani CS, Mannam AP, Cosgrove D, Silva R, Hodivala-Dilke KM, Keshamouni VG, Sudhakar A (2007) Regulation of COX-2 mediated signaling by alpha3 type IV noncollagenous domain in tumor angiogenesis. Blood 110:1168–1177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brakebusch C, Bouvard D, Stanchi F, Sakai T, Fassler R (2002) Integrins in invasive growth. J Clin Invest 109:999–1006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brakebusch C, Grose R, Quondamatteo F, Ramirez A, Jorcano JL, Pirro A, Svensson M, Herken R, Sasaki T, Timpl R, Werner S, Fassler R (2000) Skin and hair follicle integrity is crucially dependent on beta 1 integrin expression on keratinocytes. EMBO J 19:3990–4003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown EJ (2002) Integrin-associated proteins. Curr Opin Cell Biol 14:603–607

    Article  CAS  PubMed  Google Scholar 

  • Brunton VG, Frame MC (2008) Src and focal adhesion kinase as therapeutic targets in cancer. Curr Opin Pharmacol 8:427–432

    Article  CAS  PubMed  Google Scholar 

  • Cagnet S, Faraldo MM, Kreft M, Sonnenberg A, Raymond K, Glukhova MA (2014) Signaling events mediated by alpha3beta1 integrin are essential for mammary tumorigenesis. Oncogene 33:4286–4295

    Article  CAS  PubMed  Google Scholar 

  • Calderwood DA, Tai V, Di Paolo G, De Camilli P, Ginsberg MH (2004) Competition for talin results in trans-dominant inhibition of integrin activation. J Biol Chem 279:28889–28895

    Article  CAS  PubMed  Google Scholar 

  • Carney RP, Hazari S, Rojalin T, Knudson A, Gao T, Tang Y, Liu R, Viitala T, Yliperttula M, Lam KS (2017) Targeting tumor-associated exosomes with integrin-binding peptides. Adv Biosyst 1

    Google Scholar 

  • Carter WG, Kaur P, Gil SG, Gahr PJ, Wayner EA (1990a) Distinct functions for integrins a3b1 in focal adhesions and α6β4/bullous antigen in a new stable anchoring contact (SAC) of keratinocytes: relation to hemidesmosomes. J Cell Biol 111:3141–3154

    Article  CAS  PubMed  Google Scholar 

  • Carter WG, Ryan MC, Gahr PJ (1991) Epiligrin, a new cell adhesion ligand for integrin α3β1 in epithelial basement membranes. Cell 65:599–610

    Article  CAS  PubMed  Google Scholar 

  • Carter WG, Wayner EA, Bouchard TS, Kaur P (1990b) The role of integrins α2β1 and α3β1 in cell-cell and cell-substrate adhesion of human epidermal cells. J Cell Biol 110:1387–1404

    Article  CAS  PubMed  Google Scholar 

  • Cary LA, Guan JL (1999) Focal adhesion kinase in integrin-mediated signaling. Front Biosci 4:D102–D113

    Article  CAS  PubMed  Google Scholar 

  • Cavaco ACM, Rezaei M, Caliandro MF, Lima AM, Stehling M, Dhayat SA, Haier J, Brakebusch C, Eble JA (2018) The interaction between laminin-332 and alpha3beta1 Integrin determines differentiation and maintenance of CAFs, and supports invasion of pancreatic duct adenocarcinoma cells. Cancers 11

    Google Scholar 

  • Chapman HA, Wei Y, Simon DI, Waltz DA (1999) Role of urokinase receptor and caveolin in regulation of integrin signaling. Thromb Haemost 82:291–297

    Article  CAS  PubMed  Google Scholar 

  • Chattopadhyay N, Wang Z, Ashman LK, Brady-Kalnay SM, Kreidberg JA (2003) alpha3beta1 integrin-CD151, a component of the cadherin-catenin complex, regulates PTPmu expression and cell-cell adhesion. J Cell Biol 163:1351–1362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choma DP, Milano V, Pumiglia KM, DiPersio CM (2007) Integrin alpha3beta1-dependent activation of FAK/Src regulates Rac1-mediated keratinocyte polarization on laminin-5. J Invest Dermatol 127:31–40

    Article  CAS  PubMed  Google Scholar 

  • Choma DP, Pumiglia K, DiPersio CM (2004) Integrin α3β1 directs the stabilization of a polarized lamellipodium in epithelial cells through activation of Rac1. J Cell Sci 117:3947–3959

    Article  CAS  PubMed  Google Scholar 

  • Clark EA, Brugge JS (1995) Integrins and signal transduction pathways: the road taken. Science 268:233–239

    Article  CAS  PubMed  Google Scholar 

  • Clark RAF, Lanigan JM, DellaPelle P, Manseau E, Dvorak HF, Colvin RB (1982) Fibronectin and fibrin provide a provisional matrix for epidermal cell migration during wound reepithelialization. J Invest Dermatol 79:264–269

    Article  CAS  PubMed  Google Scholar 

  • Cohen-Barak E, Danial-Farran N, Khayat M, Chervinsky E, Nevet JM, Ziv M, Shalev SA (2019) A nonjunctional, nonsyndromic case of junctional epidermolysis bullosa with renal and respiratory involvement. JAMA Dermatol 155:498–500

    Article  PubMed  Google Scholar 

  • Colombo EA, Spaccini L, Volpi L, Negri G, Cittaro D, Lazarevic D, Zirpoli S, Farolfi A, Gervasini C, Cubellis MV, Larizza L (2016) Viable phenotype of ILNEB syndrome without nephrotic impairment in siblings heterozygous for unreported integrin alpha3 mutations. Orphanet J Rare Dis 11:136

    Article  PubMed  PubMed Central  Google Scholar 

  • Comoglio PM, Boccaccio C, Trusolino L (2003) Interactions between growth factor receptors and adhesion molecules: breaking the rules. Curr Opin Cell Biol 15:565–571

    Article  CAS  PubMed  Google Scholar 

  • Conti FJ, Rudling RJ, Robson A, Hodivala-Dilke KM (2003) alpha3beta1-integrin regulates hair follicle but not interfollicular morphogenesis in adult epidermis. J Cell Sci 116:2737–2747

    Article  CAS  PubMed  Google Scholar 

  • Cooper J, Giancotti FG (2019) Integrin signaling in cancer: mechanotransduction, stemness, epithelial plasticity, and therapeutic resistance. Cancer Cell 35:347–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corbi AL, Kishimoto TK, Miller LJ, Springer TA (1988) The human leukocyte adhesion glycoprotein Mac-1 (complement receptor type 3, CD11b) alpha subunit. Cloning, primary structure, and relation to the integrins, von Willebrand factor and factor B. J Biol Chem 263:12403–12411

    Article  CAS  PubMed  Google Scholar 

  • Corbi AL, Miller LJ, O’Connor K, Larson RS, Springer TA (1987) cDNA cloning and complete primary structure of the alpha subunit of a leukocyte adhesion glycoprotein, p150,95. EMBO J 6:4023–4028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cowin AJ, Adams D, Geary SM, Wright MD, Jones JC, Ashman LK (2006) Wound healing is defective in mice lacking tetraspanin CD151. J Invest Dermatol 126:680–689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cui M, Wiraja C, Chew SWT, Xu C (2021) Nanodelivery systems for topical management of skin disorders. Mol Pharm 18:491–505

    Article  CAS  PubMed  Google Scholar 

  • da Silva RG, Tavora B, Robinson SD, Reynolds LE, Szekeres C, Lamar J, Batista S, Kostourou V, Germain MA, Reynolds AR, Jones DT, Watson AR, Jones JL, Harris A, Hart IR, Iruela-Arispe ML, DiPersio CM, Kreidberg JA, Hodivala-Dilke KM (2010) Endothelial alpha3beta1-integrin represses pathological angiogenesis and sustains endothelial-VEGF. Am J Pathol 177:1534–1548

    Article  PubMed  PubMed Central  Google Scholar 

  • De Arcangelis A, Mark M, Kreidberg J, Sorokin L, Georges-Labouesse E (1999) Synergistic activities of alpha3 and alpha6 integrins are required during apical ectodermal ridge formation and organogenesis in the mouse. Development 126:3957–3968

    Article  PubMed  Google Scholar 

  • de Melker AA, Sonnenberg A (1999) Integrins: alternative splicing as a mechanism to regulate ligand binding and integrin signaling events. BioEssays 21:499–509

    Article  PubMed  Google Scholar 

  • de Melker AA, Sterk LMT, Delwel GO, Fles DLA, Daams H, Weening JJ, Sonnenberg A (1997) The A and B variants of the α3 integrin subunit: tissue distribution and functional characterization. Lab Invest 76:547–563

    PubMed  Google Scholar 

  • deHart GW, Healy KE, Jones JC (2003) The role of alpha3beta1 integrin in determining the supramolecular organization of laminin-5 in the extracellular matrix of keratinocytes. Exp Cell Res 283:67–79

    Article  CAS  PubMed  Google Scholar 

  • Del Pozo MA, Schwartz MA (2007) Rac, membrane heterogeneity, caveolin and regulation of growth by integrins. Trends Cell Biol 17:246–250

    Article  PubMed  Google Scholar 

  • Delwel GO, de Melker AA, Hogervorst F, Jaspars LH, Fles DLA, Kuikman I, Lindblom A, Paulsson M, Timpl R, Sonnenberg A (1994) Distinct and overlap** ligand specificities of the α3Aβ1 and α6Aβ1 integrins: recognition of laminin isoforms. Mol Biol Cell 5:203–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Desgrosellier JS, Cheresh DA (2010) Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 10:9–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dhavalikar P, Robinson A, Lan Z, Jenkins D, Chwatko M, Salhadar K, Jose A, Kar R, Shoga E, Kannapiran A, Cosgriff-Hernandez E (2020) Review of integrin-targeting biomaterials in tissue engineering. Adv Healthc Mater:e2000795

    Google Scholar 

  • Di Russo J, Young JL, Wegner JW, Steins T, Kessler H, Spatz JP (2021) Integrin alpha5beta1 nano-presentation regulates collective keratinocyte migration independent of substrate rigidity. Elife 10

    Google Scholar 

  • Diaz-Gonzalez F, Forsyth J, Steiner B, Ginsberg MH (1996) Trans-dominant inhibition of integrin function. Mol Biol Cell 7:1939–1951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dickreuter E, Cordes N (2017) The cancer cell adhesion resistome: mechanisms, targeting and translational approaches. Biol Chem 398:721–735

    Article  CAS  PubMed  Google Scholar 

  • DiPersio CM, Hodivala-Dilke KM, Jaenisch R, Kreidberg JA, Hynes RO (1997) alpha3beta1 Integrin is required for normal development of the epidermal basement membrane. J Cell Biol 137:729–742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DiPersio CM, Shah S, Hynes RO (1995) alpha 3A beta 1 integrin localizes to focal contacts in response to diverse extracellular matrix proteins. J Cell Sci 108(Pt 6):2321–2336

    Article  CAS  PubMed  Google Scholar 

  • DiPersio CM, Shao M, Di Costanzo L, Kreidberg JA, Hynes RO (2000a) Mouse keratinocytes immortalized with large T antigen acquire alpha3beta1 integrin-dependent secretion of MMP-9/gelatinase B. J Cell Sci 113(Pt 16):2909–2921

    Article  CAS  PubMed  Google Scholar 

  • DiPersio CM, Trevithick JE, Hynes RO (2001) Functional comparison of the alpha3A and alpha3B cytoplasmic domain variants of the chicken alpha3 integrin subunit. Exp Cell Res 268:45–60

    Article  CAS  PubMed  Google Scholar 

  • DiPersio CM, van der Neut R, Georges-Labouesse E, Kreidberg JA, Sonnenberg A, Hynes RO (2000b) alpha3beta1 and alpha6beta4 integrin receptors for laminin-5 are not essential for epidermal morphogenesis and homeostasis during skin development. J Cell Sci 113:3051–3062

    Article  CAS  PubMed  Google Scholar 

  • DiPersio CM, Zheng R, Kenney J, Van De Water L (2016) Integrin-mediated regulation of epidermal wound functions. Cell Tissue Res 365:467–482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dowling J, Yu QC, Fuchs E (1996) Beta4 integrin is required for hemidesmosome formation, cell adhesion and cell survival. J Cell Biol 134:559–572

    Article  CAS  PubMed  Google Scholar 

  • Dupont S (2016) Role of YAP/TAZ in cell-matrix adhesion-mediated signalling and mechanotransduction. Exp Cell Res 343:42–53

    Article  CAS  PubMed  Google Scholar 

  • Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, Zanconato F, Le Digabel J, Forcato M, Bicciato S, Elvassore N, Piccolo S (2011) Role of YAP/TAZ in mechanotransduction. Nature 474:179–183

    Article  CAS  PubMed  Google Scholar 

  • Duro-Castano A, Gallon E, Decker C, Vicent MJ (2017) Modulating angiogenesis with integrin-targeted nanomedicines. Adv Drug Deliv Rev 119:101–119

    Article  CAS  PubMed  Google Scholar 

  • Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650–1659

    Article  CAS  PubMed  Google Scholar 

  • Dzamba BJ, DeSimone DW (2018) Extracellular matrix (ECM) and the sculpting of embryonic tissues. Curr Top Dev Biol 130:245–274

    Article  CAS  PubMed  Google Scholar 

  • Eble JA, Bruckner P, Mayer U (2003) Vipera lebetina venom contains two disintegrins inhibiting laminin-binding beta1 integrins. J Biol Chem 278:26488–26496

    Article  CAS  PubMed  Google Scholar 

  • Elbediwy A, Vincent-Mistiaen ZI, Spencer-Dene B, Stone RK, Boeing S, Wculek SK, Cordero J, Tan EH, Ridgway R, Brunton VG, Sahai E, Gerhardt H, Behrens A, Malanchi I, Sansom OJ, Thompson BJ (2016) Integrin signalling regulates YAP and TAZ to control skin homeostasis. Development 143:1674–1687

    CAS  PubMed  PubMed Central  Google Scholar 

  • Elices MJ, Urry LA, Hemler ME (1991) Receptor functions for the integrin VLA-3: fibronectin, collagen, and laminin binding are differentially influenced by Arg-Gly-Asp peptide and by divalent cations. J Cell Biol 112:169–181

    Article  CAS  PubMed  Google Scholar 

  • Essayem S, Kovacic-Milivojevic B, Baumbusch C, McDonagh S, Dolganov G, Howerton K, Larocque N, Mauro T, Ramirez A, Ramos DM, Fisher SJ, Jorcano JL, Beggs HE, Reichardt LF, Ilic D (2005) Hair cycle and wound healing in mice with a keratinocyte-restricted deletion of FAK. Oncogene

    Google Scholar 

  • Fane ME, Chhabra Y, Smith AG, Sturm RA (2019) BRN2, a POUerful driver of melanoma phenotype switching and metastasis. Pigment Cell Melanoma Res 32:9–24

    Article  CAS  PubMed  Google Scholar 

  • Fedele C, Singh A, Zerlanko BJ, Iozzo RV, Languino LR (2015) The alphavbeta6 integrin is transferred intercellularly via exosomes. J Biol Chem 290:4545–4551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferraris GM, Schulte C, Buttiglione V, De Lorenzi V, Piontini A, Galluzzi M, Podesta A, Madsen CD, Sidenius N (2014) The interaction between uPAR and vitronectin triggers ligand-independent adhesion signalling by integrins. EMBO J 33:2458–2472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • ffrench-Constant C, Colognato H (2004) Integrins: versatile integrators of extracellular signals. Trends Cell Biol 14:678–686

    Article  CAS  PubMed  Google Scholar 

  • Fitzgerald LA, Poncz M, Steiner B, Rall SC Jr, Bennett JS, Phillips DR (1987) Comparison of cDNA-derived protein sequences of the human fibronectin and vitronectin receptor alpha-subunits and platelet glycoprotein IIb. Biochemistry 26:8158–8165

    Article  CAS  PubMed  Google Scholar 

  • Fradet Y, Cordon-Cardo C, Thomson T, Daly ME, Whitmore WF Jr, Lloyd KO, Melamed MR, Old LJ (1984) Cell surface antigens of human bladder cancer defined by mouse monoclonal antibodies. Proc Natl Acad Sci U S A 81:224–228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frank DE, Carter WG (2004) Laminin 5 deposition regulates keratinocyte polarization and persistent migration. J Cell Sci 117:1351–1363

    Article  CAS  PubMed  Google Scholar 

  • Frisch SM, Screaton RA (2001) Anoikis mechanisms. Curr Opin Cell Biol 13:555–562

    Article  CAS  PubMed  Google Scholar 

  • Fuchs E (2008) Skin stem cells: rising to the surface. J Cell Biol 180:273–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gagnoux-Palacios L, Allegra M, Spirito F, Pommeret O, Romero C, Ortonne JP, Meneguzzi G (2001) The short arm of the laminin gamma2 chain plays a pivotal role in the incorporation of laminin 5 into the extracellular matrix and in cell adhesion. J Cell Biol 153:835–850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gehlsen KR, Dickerson K, Argraves WS, Engvall E, Ruoslahti E (1989) Subunit structure of a laminin-binding integrin and localization of its binding site on laminin. J Biol Chem 264:19034–19038

    Article  CAS  PubMed  Google Scholar 

  • Georges-Labouesse E, Messaddeq N, Yehia G, Cadalbert L, Dierich A, Le Meur M (1996) Absence of integrin alpha 6 leads to epidermolysis bullosa and neonatal death in mice. Nat Genet 13:370–373

    Article  CAS  PubMed  Google Scholar 

  • Ghahary A, Ghaffari A (2007) Role of keratinocyte-fibroblast cross-talk in development of hypertrophic scar. Wound Repair Regen 15(Suppl 1):S46–S53

    Article  PubMed  Google Scholar 

  • Ghosh S, Brown R, Jones JC, Ellerbroek SM, Stack MS (2000) Urinary-type plasminogen activator (uPA) expression and uPA receptor localization are regulated by alpha 3beta 1 integrin in oral keratinocytes. J Biol Chem 275:23869–23876

    Article  CAS  PubMed  Google Scholar 

  • Ghosh S, Johnson JJ, Sen R, Mukhopadhyay S, Liu Y, Zhang F, Wei Y, Chapman HA, Stack MS (2006) Functional relevance of urinary-type plasminogen activator receptor-alpha3beta1 integrin association in proteinase regulatory pathways. J Biol Chem 281:13021–13029

    Article  CAS  PubMed  Google Scholar 

  • Ghosh S, Koblinski J, Johnson J, Liu Y, Ericsson A, Davis JW, Shi Z, Ravosa MJ, Crawford S, Frazier S, Stack MS (2010) Urinary-type plasminogen activator receptor/alpha 3 beta 1 integrin signaling, altered gene expression, and oral tumor progression. Mol Cancer Res 8:145–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giannelli G, Fransvea E, Marinosci F, Bergamini C, Colucci S, Schiraldi O, Antonaci S (2002) Transforming growth factor-beta1 triggers hepatocellular carcinoma invasiveness via alpha3beta1 integrin. Am J Pathol 161:183–193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gill SE, Parks WC (2008) Metalloproteinases and their inhibitors: regulators of wound healing. Int J Biochem Cell Biol 40:1334–1347

    Article  CAS  PubMed  Google Scholar 

  • Glinskii OV, Li F, Wilson LS, Barnes S, Rittenhouse-Olson K, Barchi JJ Jr, Pienta KJ, Glinsky VV (2014) Endothelial integrin alpha3beta1 stabilizes carbohydrate-mediated tumor/endothelial cell adhesion and induces macromolecular signaling complex formation at the endothelial cell membrane. Oncotarget 5:1382–1389

    Article  PubMed  PubMed Central  Google Scholar 

  • Goldfinger LE, Hopkinson SB, deHart GW, Collawn S, Couchman JR, Jones JCR (1999) The α3 laminin subunit, α6β4 and α3β1 integrin coordinately regulate wound healing in cultured epithelial cells in the skin. J Cell Sci 112:2615–2629

    Article  CAS  PubMed  Google Scholar 

  • Goldfinger LE, Stack MS, Jones JCR (1998) Processing of laminin-5 and its functional consequences: role of plasmin and tissue-type plasminogen activator. J Cell Biol 141:255–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzales M, Haan K, Baker SE, Fitchmun M, Todorov I, Weitzman S, Jones JCR (1999) A cell signal pathway involving laminin-5, α3β1 integrin, and mitogen-activated protein kinase can regulate epithelial cell proliferation. Mol Biol Cell 10:259–270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez AM, Bhattacharya R, deHart GW, Jones JC (2010) Transdominant regulation of integrin function: mechanisms of crosstalk. Cell Signal 22:578–583

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez AM, Gonzales M, Herron GS, Nagavarapu U, Hopkinson SB, Tsuruta D, Jones JC (2002) Complex interactions between the laminin alpha 4 subunit and integrins regulate endothelial cell behavior in vitro and angiogenesis in vivo. Proc Natl Acad Sci U S A 99:16075–16080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goodman SL, Picard M (2012) Integrins as therapeutic targets. Trends Pharmacol Sci 33:405–412

    Article  CAS  PubMed  Google Scholar 

  • Grenache DG, Zhang Z, Wells LE, Santoro SA, Davidson JM, Zutter MM (2007) Wound healing in the alpha2beta1 integrin-deficient mouse: altered keratinocyte biology and dysregulated matrix metalloproteinase expression. J Invest Dermatol 127:455–466

    Article  CAS  PubMed  Google Scholar 

  • Grose R, Hutter C, Bloch W, Thorey I, Watt FM, Fassler R, Brakebusch C, Werner S (2002) A crucial role of beta 1 integrins for keratinocyte migration in vitro and during cutaneous wound repair. Development 129:2303–2315

    Article  CAS  PubMed  Google Scholar 

  • Guidetti GF, Torti M, Canobbio I (2019) Focal adhesion kinases in platelet function and thrombosis. Arterioscler Thromb Vasc Biol 39:857–868

    Article  CAS  PubMed  Google Scholar 

  • Guo W, Giancotti FG (2004) Integrin signalling during tumour progression. Nat Rev Mol Cell Biol 5:816–826

    Article  CAS  PubMed  Google Scholar 

  • Gupta SK, Oommen S, Aubry MC, Williams BP, Vlahakis NE (2013) Integrin alpha9beta1 promotes malignant tumor growth and metastasis by potentiating epithelial-mesenchymal transition. Oncogene 32:141–150

    Article  CAS  PubMed  Google Scholar 

  • Hamelers IH, Olivo C, Mertens AE, Pegtel DM, van der Kammen RA, Sonnenberg A, Collard JG (2005) The Rac activator Tiam1 is required for α3β1-mediated laminin-5 deposition, cell spreading, and cell migration. J Cell Biol 171:871–881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamidi H, Ivaska J (2018) Every step of the way: integrins in cancer progression and metastasis. Nat Rev Cancer 18:533–548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Has C, Fischer J (2019) Inherited epidermolysis bullosa: new diagnostics and new clinical phenotypes. Exp Dermatol 28:1146–1152

    Article  PubMed  Google Scholar 

  • Has C, Sparta G, Kiritsi D, Weibel L, Moeller A, Vega-Warner V, Waters A, He Y, Anikster Y, Esser P, Straub BK, Hausser I, Bockenhauer D, Dekel B, Hildebrandt F, Bruckner-Tuderman L, Laube GF (2012) Integrin alpha3 mutations with kidney, lung, and skin disease. N Engl J Med 366:1508–1514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He Y, Balasubramanian M, Humphreys N, Waruiru C, Brauner M, Kohlhase J, O’Reilly R, Has C (2016) Intronic ITGA3 mutation impacts splicing regulation and causes interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa. J Invest Dermatol 136:1056–1059

    Article  CAS  PubMed  Google Scholar 

  • He Y, Thriene K, Boerries M, Hausser I, Franzke CW, Busch H, Dengjel J, Has C (2018) Constitutional absence of epithelial integrin alpha3 impacts the composition of the cellular microenvironment of ILNEB keratinocytes. Matrix Biol 74:62–76

    Article  CAS  PubMed  Google Scholar 

  • Hemler ME (2005) Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol 6:801–811

    Article  CAS  PubMed  Google Scholar 

  • Hemler ME, Hoff J, Li Q, Yang XH (2013) Renal disease appears not to affect carcinogenesis in CD151-null mice. Oncogene 32:4458

    Article  CAS  PubMed  Google Scholar 

  • Hemler ME, Huang C, Schwarz L (1987) The VLA protein family. J Biol Chem 262:3300–3309

    Article  CAS  PubMed  Google Scholar 

  • Hertle MD, Adams JC, Watt FM (1991) Integrin expression during human epidermal development in vivo and in vitro. Development 112:193–206

    Article  CAS  PubMed  Google Scholar 

  • Hight-Warburton W, Felix R, Burton A, Maple H, Chegkazi MS, Steiner RA, McGrath JA, Parsons M (2021) alpha4/alpha9 integrins coordinate epithelial cell migration through local suppression of MAP kinase signaling pathways. Front Cell Dev Biol 9:750771

    Article  PubMed  PubMed Central  Google Scholar 

  • Hobbs RM, Watt FM (2003) Regulation of interleukin-1alpha expression by integrins and epidermal growth factor receptor in keratinocytes from a mouse model of inflammatory skin disease. J Biol Chem 278:19798–19807

    Article  CAS  PubMed  Google Scholar 

  • Hodivala-Dilke KM, DiPersio CM, Kreidberg JA, Hynes RO (1998) Novel roles for alpha3beta1 integrin as a regulator of cytoskeletal assembly and as a trans-dominant inhibitor of integrin receptor function in mouse keratinocytes. J Cell Biol 142:1357–1369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hodivala-Dilke KM, Reynolds AR, Reynolds LE (2003) Integrins in angiogenesis: multitalented molecules in a balancing act. Cell Tissue Res 314:131–144

    Article  CAS  PubMed  Google Scholar 

  • Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S, Singh S, Williams C, Soplop N, Uryu K, Pharmer L, King T, Bojmar L, Davies AE, Ararso Y, Zhang T, Zhang H, Hernandez J, Weiss JM, Dumont-Cole VD, Kramer K, Wexler LH, Narendran A, Schwartz GK, Healey JH, Sandstrom P, Labori KJ, Kure EH, Grandgenett PM, Hollingsworth MA, de Sousa M, Kaur S, Jain M, Mallya K, Batra SK, Jarnagin WR, Brady MS, Fodstad O, Muller V, Pantel K, Minn AJ, Bissell MJ, Garcia BA, Kang Y, Rajasekhar VK, Ghajar CM, Matei I, Peinado H, Bromberg J, Lyden D (2015) Tumour exosome integrins determine organotropic metastasis. Nature 527:329–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu JK, Du W, Shelton SJ, Oldham MC, DiPersio CM, Klein OD (2017) An FAK-YAP-mTOR signaling axis regulates stem cell-based tissue renewal in mice. Cell Stem Cell 21:91–106 e106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang X, Griffiths M, Wu J, Farese RV Jr, Sheppard D (2000) Normal development, wound healing, and adenovirus susceptibility in beta5-deficient mice. Mol Cell Biol 20:755–759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hynes RO (1987) Integrins: a family of cell surface receptors. Cell 48:549–554

    Article  CAS  PubMed  Google Scholar 

  • Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25

    Article  CAS  PubMed  Google Scholar 

  • Hynes RO (2002a) Integrins: bidirectional, allosteric signaling machines. Cell 110:673–687

    Article  CAS  PubMed  Google Scholar 

  • Hynes RO (2002b) A reevaluation of integrins as regulators of angiogenesis. Nat Med 8:918–921

    Article  CAS  PubMed  Google Scholar 

  • Hynes RO (2004) The emergence of integrins: a personal and historical perspective. Matrix Biol 23:333–340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hynes RO, Marcantonio EE, Stepp MA, Urry LA, Yee GH (1989) Integrin heterodimer and receptor complexity in avian and mammalian cells. J Cell Biol 109:409–420

    Article  CAS  PubMed  Google Scholar 

  • Hynes RO, Zhao Q (2000) The evolution of cell adhesion. J Cell Biol 150:F89–F95

    Article  CAS  PubMed  Google Scholar 

  • Ishii J, Sato H, Sakaeda M, Shishido-Hara Y, Hiramatsu C, Kamma H, Shimoyamada H, Fujiwara M, Endo T, Aoki I, Yazawa T (2013) POU domain transcription factor BRN2 is crucial for expression of ASCL1, ND1 and neuroendocrine marker molecules and cell growth in small cell lung cancer. Pathol Int 63:158–168

    Article  CAS  PubMed  Google Scholar 

  • Ito M, Liu Y, Yang Z, Nguyen J, Liang F, Morris RJ, Cotsarelis G (2005) Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nat Med 11:1351–1354

    Article  CAS  PubMed  Google Scholar 

  • Iyer V, Pumiglia K, DiPersio CM (2005) α3β1 integrin regulates MMP-9 mRNA stability in immortalized keratinocytes: a novel mechanism of integrin-mediated MMP gene expression. J Cell Sci 118:1185–1195

    Article  CAS  PubMed  Google Scholar 

  • Janes SM, Watt FM (2006) New roles for integrins in squamous-cell carcinoma. Nat Rev Cancer 6:175–183

    Article  CAS  PubMed  Google Scholar 

  • Jones PH, Harper S, Watt FM (1995) Stem cell patterning and fate in human epidermis. Cell 80:83–93

    Article  CAS  PubMed  Google Scholar 

  • Jones PH, Watt FM (1993) Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell 73:713–724

    Article  CAS  PubMed  Google Scholar 

  • Kadry YA, Calderwood DA (2020) Chapter 22: Structural and signaling functions of integrins. Biochim Biophys Acta Biomembr 1862:183206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamoshida G, Matsuda A, Katabami K, Kato T, Mizuno H, Sekine W, Oku T, Itoh S, Tsuiji M, Hattori Y, Maitani Y, Tsuji T (2012) Involvement of transcription factor Ets-1 in the expression of the alpha3 integrin subunit gene. FEBS J 279:4535–4546

    Article  CAS  PubMed  Google Scholar 

  • Kang HJ, Chen N, Dash BC, Hsia HC, Berthiaume F (2021) Self-assembled nanomaterials for chronic skin wound healing. Adv Wound Care (New Rochelle) 10:221–233

    Article  PubMed  Google Scholar 

  • Karamatic Crew V, Burton N, Kagan A, Green CA, Levene C, Flinter F, Brady RL, Daniels G, Anstee DJ (2004) CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin. Blood 104:2217–2223

    Article  PubMed  Google Scholar 

  • Katabami K, Mizuno H, Sano R, Saito Y, Ogura M, Itoh S, Tsuji T (2005) Transforming growth factor-beta1 upregulates transcription of alpha3 integrin gene in hepatocellular carcinoma cells via Ets-transcription factor-binding motif in the promoter region. Clin Exp Metastasis 22:539–548

    Article  CAS  PubMed  Google Scholar 

  • Kaufmann R, Frösch D, Westphal C, Weber L, Klein CE (1989) Integrin VLA-3: ultrastructural localization at cell-cell contact sites of human cell cultures. J Cell Biol 109:1807–1815

    Article  CAS  PubMed  Google Scholar 

  • Kawataki T, Yamane T, Naganuma H, Rousselle P, Anduren I, Tryggvason K, Patarroyo M (2007) Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness: evidence for a role of alpha5-laminin(s) and alpha3beta1 integrin. Exp Cell Res 313:3819–3831

    Article  CAS  PubMed  Google Scholar 

  • Kazarov AR, Yang X, Stipp CS, Sehgal B, Hemler ME (2002) An extracellular site on tetraspanin CD151 determines alpha 3 and alpha 6 integrin-dependent cellular morphology. J Cell Biol 158:1299–1309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ke FY, Chen WY, Lin MC, Hwang YC, Kuo KT, Wu HC (2020) Novel monoclonal antibody against integrin alpha3 shows therapeutic potential for ovarian cancer. Cancer Sci 111:3478–3492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kechagia JZ, Ivaska J, Roca-Cusachs P (2019) Integrins as biomechanical sensors of the microenvironment. Nat Rev Mol Cell Biol 20:457–473

    Article  CAS  PubMed  Google Scholar 

  • Kenney J, Ndoye A, Lamar JM, DiPersio CM (2021) Comparative use of CRISPR and RNAi to modulate integrin alpha3beta1 in triple negative breast cancer cells reveals that some pro-invasive/pro-metastatic alpha3beta1 functions are independent of global regulation of the transcriptome. PLoS One 16:e0254714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim JP, Zhang K, Kramer RH, Schall TJ, Woodley DT (1992) Integrin receptors and RGD sequences in human keratinocyte migration: unique anti-migratory function of alpha 3 beta 1 epiligrin receptor. J Invest Dermatol 98:764–770

    Article  CAS  PubMed  Google Scholar 

  • Kim KK, Wei Y, Szekeres C, Kugler MC, Wolters PJ, Hill ML, Frank JA, Brumwell AN, Wheeler SE, Kreidberg JA, Chapman HA (2009a) Epithelial cell alpha3beta1 integrin links beta-catenin and Smad signaling to promote myofibroblast formation and pulmonary fibrosis. J Clin Invest 119:213–224

    CAS  PubMed  Google Scholar 

  • Kim Y, Kugler MC, Wei Y, Kim KK, Li X, Brumwell AN, Chapman HA (2009b) Integrin alpha3beta1-dependent beta-catenin phosphorylation links epithelial Smad signaling to cell contacts. J Cell Biol 184:309–322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kinyo A, Kovacs AL, Degrell P, Kalman E, Nagy N, Karpati S, Gyulai R, Saeidian AH, Youssefian L, Vahidnezhad H, Uitto J (2021) Homozygous ITGA3 missense mutation in adults in a family with syndromic epidermolysis bullosa (ILNEB) without pulmonary involvement. J Invest Dermatol 141:2752–2756

    Article  CAS  PubMed  Google Scholar 

  • Kivirikko S, McGrath JA, Baudoin C, Aberdam D, Ciatti S, Dunnill MG, McMillan JR, Eady RA, Ortonne JP, Meneguzzi G et al (1995) A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in lethal (Herlitz) junctional epidermolysis bullosa. Hum Mol Genet 4:959–962

    Article  CAS  PubMed  Google Scholar 

  • Klinowska TC, Alexander CM, Georges-Labouesse E, Van der Neut R, Kreidberg JA, Jones CJ, Sonnenberg A, Streuli CH (2001) Epithelial development and differentiation in the mammary gland is not dependent on alpha 3 or alpha 6 integrin subunits. Dev Biol 233:449–467

    Article  CAS  PubMed  Google Scholar 

  • Kochar AS, Madhavan M, Manjila S, Scoco A, Belle VK, Geertman RT (2018) Contemporary updates on clinical trials of antiangiogenic agents in the treatment of glioblastoma multiforme. Asian J Neurosurg 13:546–554

    Article  PubMed  PubMed Central  Google Scholar 

  • Koivisto L, Heino J, Hakkinen L, Larjava H (2014) Integrins in wound healing. Adv Wound Care (New Rochelle) 3:762–783

    Article  PubMed  PubMed Central  Google Scholar 

  • Kostourou V, Lechertier T, Reynolds LE, Lees DM, Baker M, Jones DT, Tavora B, Ramjaun AR, Birdsey GM, Robinson SD, Parsons M, Randi AM, Hart IR, Hodivala-Dilke K (2013) FAK-heterozygous mice display enhanced tumour angiogenesis. Nat Commun 4:2020

    Article  PubMed  Google Scholar 

  • Kreidberg JA (2000) Functions of a3b1 integrin. Curr Opin Cell Biol 12:548–553

    Article  CAS  PubMed  Google Scholar 

  • Kreidberg JA, Donovan MJ, Goldstein SL, Rennke H, Shepherd K, Jones RC, Jaenisch R (1996) Alpha 3 beta 1 integrin has a crucial role in kidney and lung organogenesis. Development 122:3537–3547

    Article  CAS  PubMed  Google Scholar 

  • Kunneken K, Pohlentz G, Schmidt-Hederich A, Odenthal U, Smyth N, Peter-Katalinic J, Bruckner P, Eble JA (2004) Recombinant human laminin-5 domains. Effects of heterotrimerization, proteolytic processing, and N-glycosylation on alpha3beta1 integrin binding. J Biol Chem 279:5184–5193

    PubMed  Google Scholar 

  • Kusuma N, Denoyer D, Eble JA, Redvers RP, Parker BS, Pelzer R, Anderson RL, Pouliot N (2012) Integrin-dependent response to laminin-511 regulates breast tumor cell invasion and metastasis. Int J Cancer 130:555–566

    Article  CAS  PubMed  Google Scholar 

  • LaFlamme SE, Akiyama SK, Yamada KM (1992) Regulation of fibronectin receptor distribution. J Cell Biol 117:437–447

    Article  CAS  PubMed  Google Scholar 

  • LaFoya B, Munroe JA, Miyamoto A, Detweiler MA, Crow JJ, Gazdik T, Albig AR (2018) Beyond the matrix: the many non-ECM ligands for integrins. Int J Mol Sci 19

    Google Scholar 

  • Lamar J, DiPersio CM (2011) Roles of integrins in the development and progression of squamous cell carcinomas. In: Glick A, Van Waes C (eds) Signaling pathways in squamous cancer. Springer, New York, NY, pp 21–52

    Chapter  Google Scholar 

  • Lamar JM, Iyer V, DiPersio CM (2008a) Integrin alpha3beta1 potentiates TGFbeta-mediated induction of MMP-9 in immortalized keratinocytes. J Invest Dermatol 128:575–586

    Article  CAS  PubMed  Google Scholar 

  • Lamar JM, Pumiglia KM, DiPersio CM (2008b) An immortalization-dependent switch in integrin function up-regulates MMP-9 to enhance tumor cell invasion. Cancer Res 68:7371–7379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lamar JM, Stern P, Liu H, Schindler JW, Jiang ZG, Hynes RO (2012) The Hippo pathway target, YAP, promotes metastasis through its TEAD-interaction domain. Proc Natl Acad Sci U S A 109:E2441–E2450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lampe PD, Nguyen BP, Gil S, Usui M, Olerud J, Takada Y, Carter WG (1998) Cellular interactions of integrin α3β1 with laminin 5 promotes gap junctional communication. J Cell Biol 143:1735–1747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lasinska I, Mackiewicz J (2019) Integrins as A new target for cancer treatment. Anticancer Agents Med Chem 19:580–586

    Article  CAS  PubMed  Google Scholar 

  • Lee MJ, Ran Byun M, Furutani-Seiki M, Hong JH, Jung HS (2014) YAP and TAZ regulate skin wound healing. J Invest Dermatol 134:518–525

    Article  CAS  PubMed  Google Scholar 

  • Legate KR, Fassler R (2009) Mechanisms that regulate adaptor binding to beta-integrin cytoplasmic tails. J Cell Sci 122:187–198

    Article  CAS  PubMed  Google Scholar 

  • Li C, Yang Z, Du Y, Tang H, Chen J, Hu D, Fan Z (2014) BCMab1, a monoclonal antibody against aberrantly glycosylated integrin alpha3beta1, has potent antitumor activity of bladder cancer in vivo. Clin Cancer Res 20:4001–4013

    Article  CAS  PubMed  Google Scholar 

  • Li N, Zhang Y, Naylor MJ, Schatzmann F, Maurer F, Wintermantel T, Schuetz G, Mueller U, Streuli CH, Hynes NE (2005) Beta1 integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli. EMBO J 24:1942–1953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li P, Silvis MR, Honaker Y, Lien WH, Arron ST, Vasioukhin V (2016) alphaE-catenin inhibits a Src-YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway. Genes Dev 30:798–811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Q, Yang XH, Xu F, Sharma C, Wang HX, Knoblich K, Rabinovitz I, Granter SR, Hemler ME (2013) Tetraspanin CD151 plays a key role in skin squamous cell carcinoma. Oncogene 32:1772–1783

    Article  CAS  PubMed  Google Scholar 

  • Lietha D, Izard T (2020) Roles of membrane domains in integrin-mediated cell adhesion. Int J Mol Sci 21

    Google Scholar 

  • Lin C, Yao E, Chuang PT (2015) A conserved MST1/2-YAP axis mediates Hippo signaling during lung growth. Dev Biol 403:101–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Litjens SH, de Pereda JM, Sonnenberg A (2006) Current insights into the formation and breakdown of hemidesmosomes. Trends Cell Biol 16:376–383

    Article  CAS  PubMed  Google Scholar 

  • Liu F, Lagares D, Choi KM, Stopfer L, Marinkovic A, Vrbanac V, Probst CK, Hiemer SE, Sisson TH, Horowitz JC, Rosas IO, Fredenburgh LE, Feghali-Bostwick C, Varelas X, Tager AM, Tschumperlin DJ (2015) Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis. Am J Physiol Lung Cell Mol Physiol 308:L344–L357

    Article  CAS  PubMed  Google Scholar 

  • Liu S, Calderwood DA, Ginsberg MH (2000) Integrin cytoplasmic domain-binding proteins. J Cell Sci 113:3563–3571

    Article  CAS  PubMed  Google Scholar 

  • Liu WF, Zuo HJ, Chai BL, Peng D, Fei YJ, Lin JY, Yu XH, Wang DW, Liu ZX (2011) Role of tetraspanin CD151-alpha3/alpha6 integrin complex: implication in angiogenesis CD151-integrin complex in angiogenesis. Int J Biochem Cell Biol 43:642–650

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Chattopadhyay N, Qin S, Szekeres C, Vasylyeva T, Mahoney ZX, Taglienti M, Bates CM, Chapman HA, Miner JH, Kreidberg JA (2009) Coordinate integrin and c-Met signaling regulate Wnt gene expression during epithelial morphogenesis. Development 136:843–853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Shi K, Chen Y, Wu X, Chen Z, Cao K, Tao Y, Chen X, Liao J, Zhou J (2021a) Exosomes and their role in cancer progression. Front Oncol 11:639159

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Yue Z, Wang H, Li M, Wu X, Lin H, Han W, Lan S, Sun L (2021b) A novel ITGA3 homozygous splice mutation in an ILNEB syndrome child with slow progression. Clin Chim Acta 523:430–436

    Article  CAS  PubMed  Google Scholar 

  • Longmate W, DiPersio CM (2017) Beyond adhesion: emerging roles for integrins in control of the tumor microenvironment. F1000Res 6:1612

    Article  PubMed  PubMed Central  Google Scholar 

  • Longmate WM (2020) Kee** a secretome: emerging roles for epithelial integrins in controlling a stroma-supportive secretome. J Dermatol Skin Sci 2:13–20

    Google Scholar 

  • Longmate WM, DiPersio CM (2014) Integrin regulation of epidermal functions in wounds. Adv Wound Care (New Rochelle) 3:229–246

    Article  PubMed  Google Scholar 

  • Longmate WM, Lyons SP, Chittur SV, Pumiglia KM, Van De Water L, DiPersio CM (2017) Suppression of integrin alpha3beta1 by alpha9beta1 in the epidermis controls the paracrine resolution of wound angiogenesis. J Cell Biol 216:1473–1488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Longmate WM, Lyons SP, DeFreest L, Van De Water L, DiPersio CM (2018) Opposing roles of epidermal integrins alpha3beta1 and alpha9beta1 in regulation of mTLD/BMP-1-mediated laminin-gamma2 processing during wound healing. J Invest Dermatol 138:444–451

    Article  CAS  PubMed  Google Scholar 

  • Longmate WM, Miskin RP, Van De Water L, DiPersio CM (2021a) Epidermal Integrin α3β1 Regulates Tumor-Derived Proteases BMP-1, Matrix Metalloprotease-9, and Matrix Metalloprotease-3. JID Innovations 1

    Google Scholar 

  • Longmate WM, Monichan R, Chu ML, Tsuda T, Mahoney MG, DiPersio CM (2014) Reduced fibulin-2 contributes to loss of basement membrane integrity and skin blistering in mice lacking integrin alpha3beta1 in the epidermis. J Invest Dermatol 134:1609–1617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Longmate WM, Varney S, Power D, Miskin RP, Anderson KE, DeFreest L, Van De Water L, DiPersio CM (2021b) Integrin alpha3beta1 on tumor keratinocytes is essential to maintain tumor growth and promotes a tumor-supportive keratinocyte secretome. J Invest Dermatol 141:142–151 e146

    Article  CAS  PubMed  Google Scholar 

  • Lubin FD, Segal M, McGee DW (2003) Regulation of epithelial cell cytokine responses by the alpha3beta1 integrin. Immunology 108:204–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luque JM (2004) Integrin and the Reelin-Dab1 pathway: a sticky affair? Brain Res Dev Brain Res 152:269–271

    Article  CAS  PubMed  Google Scholar 

  • Maldonado H, Hagood JS (2021) Cooperative signaling between integrins and growth factor receptors in fibrosis. J Mol Med (Berl) 99:213–224

    Article  CAS  PubMed  Google Scholar 

  • Manohar A, Shome SG, Lamar J, Stirling L, Iyer V, Pumiglia K, DiPersio CM (2004) Alpha 3 beta 1 integrin promotes keratinocyte cell survival through activation of a MEK/ERK signaling pathway. J Cell Sci 117:4043–4054

    Article  CAS  PubMed  Google Scholar 

  • Marcucci F, Bellone M, Caserta CA, Corti A (2014) Pushing tumor cells towards a malignant phenotype: stimuli from the microenvironment, intercellular communications and alternative roads. Int J Cancer 135:1265–1276

    Article  CAS  PubMed  Google Scholar 

  • Margadant C, Charafeddine RA, Sonnenberg A (2010) Unique and redundant functions of integrins in the epidermis. FASEB J 24:4133–4152

    Article  CAS  PubMed  Google Scholar 

  • Margadant C, Raymond K, Kreft M, Sachs N, Janssen H, Sonnenberg A (2009) Integrin alpha3beta1 inhibits directional migration and wound re-epithelialization in the skin. J Cell Sci 122:278–288

    Article  CAS  PubMed  Google Scholar 

  • Margadant C, Sonnenberg A (2010) Integrin-TGF-beta crosstalk in fibrosis, cancer and wound healing. EMBO Rep 11:97–105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mascre G, Dekoninck S, Drogat B, Youssef KK, Brohee S, Sotiropoulou PA, Simons BD, Blanpain C (2012) Distinct contribution of stem and progenitor cells to epidermal maintenance. Nature 489:257–262

    Article  CAS  PubMed  Google Scholar 

  • McCawley LJ, Matrisian LM (2001) Matrix metalloproteinases: they’re not just for matrix anymore! Curr Opin Cell Biol 13:534–540

    Article  CAS  PubMed  Google Scholar 

  • McLean GW, Brown K, Arbuckle MI, Wyke AW, Pikkarainen T, Ruoslahti E, Frame MC (2001) Decreased focal adhesion kinase suppresses papilloma formation during experimental mouse skin carcinogenesis. Cancer Res 61:8385–8389

    CAS  PubMed  Google Scholar 

  • McLean GW, Komiyama NH, Serrels B, Asano H, Reynolds L, Conti F, Hodivala-Dilke K, Metzger D, Chambon P, Grant SG, Frame MC (2004) Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression. Genes Dev 18:2998–3003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meng X, Klement JF, Leperi DA, Birk DE, Sasaki T, Timpl R, Uitto J, Pulkkinen L (2003) Targeted inactivation of murine laminin gamma2-chain gene recapitulates human junctional epidermolysis bullosa. J Invest Dermatol 121:720–731

    Article  CAS  PubMed  Google Scholar 

  • Menko AS, Kreidberg JA, Ryan TT, Van Bockstaele E, Kukuruzinska MA (2001) Loss of alpha3beta1 integrin function results in an altered differentiation program in the mouse submandibular gland. Dev Dyn 220:337–349

    Article  CAS  PubMed  Google Scholar 

  • Mezu-Ndubuisi OJ, Maheshwari A (2021) The role of integrins in inflammation and angiogenesis. Pediatr Res 89:1619–1626

    Article  PubMed  Google Scholar 

  • Miskin RP, Warren JSA, Ndoye A, Wu L, Lamar JM, DiPersio CM (2021) Integrin alpha3beta1 promotes invasive and metastatic properties of breast cancer cells through induction of the Brn-2 transcription factor. Cancers 13

    Google Scholar 

  • Missan DS, Chittur SV, DiPersio CM (2014) Regulation of fibulin-2 gene expression by integrin alpha3beta1 contributes to the invasive phenotype of transformed keratinocytes. J Invest Dermatol 134:2418–2427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Missan DS, DiPersio M (2012) Integrin control of tumor invasion. Crit Rev Eukaryot Gene Expr 22:309–324

    Article  CAS  PubMed  Google Scholar 

  • Missan DS, Mitchell K, Subbaram S, DiPersio CM (2015) Integrin alpha3beta1 signaling through MEK/ERK determines alternative polyadenylation of the MMP-9 mRNA transcript in immortalized mouse keratinocytes. PLoS One 10:e0119539

    Article  PubMed  PubMed Central  Google Scholar 

  • Mitchell K, Svenson KB, Longmate WM, Gkirtzimanaki K, Sadej R, Wang X, Zhao J, Eliopoulos AG, Berditchevski F, DiPersio CM (2010) Suppression of integrin alpha3beta1 in breast cancer cells reduces cyclooxygenase-2 gene expression and inhibits tumorigenesis, invasion, and cross-talk to endothelial cells. Cancer Res 70:6359–6367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mitchell K, Szekeres C, Milano V, Svenson KB, Nilsen-Hamilton M, Kreidberg JA, DiPersio CM (2009) Alpha3beta1 integrin in epidermis promotes wound angiogenesis and keratinocyte-to-endothelial-cell crosstalk through the induction of MRP3. J Cell Sci 122:1778–1787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mitra SK, Schlaepfer DD (2006) Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol 18:516–523

    Article  CAS  PubMed  Google Scholar 

  • Morini M, Mottolese M, Ferrari N, Ghiorzo F, Buglioni S, Mortarini R, Noonan DM, Natali PG, Albini A (2000) The alpha 3 beta 1 integrin is associated with mammary carcinoma cell metastasis, invasion, and gelatinase B (MMP-9) activity. Int J Cancer 87:336–342

    Article  CAS  PubMed  Google Scholar 

  • Moroishi T, Hansen CG, Guan KL (2015) The emerging roles of YAP and TAZ in cancer. Nat Rev Cancer 15:73–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muir AM, Massoudi D, Nguyen N, Keene DR, Lee SJ, Birk DE, Davidson JM, Marinkovich MP, Greenspan DS (2016) BMP1-like proteinases are essential to the structure and wound healing of skin. Matrix Biol 56:114–131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Navdaev A, Heitmann V, Desantana Evangelista K, Morgelin M, Wegener J, Eble JA (2008) The C-terminus of the gamma 2 chain but not of the beta 3 chain of laminin-332 is indirectly but indispensably necessary for integrin-mediated cell reactions. Exp Cell Res 314:489–497

    Article  CAS  PubMed  Google Scholar 

  • Naylor MJ, Li N, Cheung J, Lowe ET, Lambert E, Marlow R, Wang P, Schatzmann F, Wintermantel T, Schuetz G, Clarke AR, Mueller U, Hynes NE, Streuli CH (2005) Ablation of beta1 integrin in mammary epithelium reveals a key role for integrin in glandular morphogenesis and differentiation. J Cell Biol 171:717–728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ndoye A, Miskin RP, DiPersio CM (2021) Integrin alpha3beta1 represses reelin expression in breast cancer cells to promote invasion. Cancers 13

    Google Scholar 

  • Nguyen BP, Ren XD, Schwartz MA, Carter WG (2001) Ligation of integrin alpha 3beta 1 by laminin 5 at the wound edge activates Rho-dependent adhesion of leading keratinocytes on collagen. J Biol Chem 276:43860–43870

    Article  CAS  PubMed  Google Scholar 

  • Nguyen BP, Ryan MC, Gil SG, Carter WG (2000) Deposition of laminin 5 in epidermal wounds regulates integrin signaling and adhesion. Curr Opin Cell Biol 12:554–562

    Article  CAS  PubMed  Google Scholar 

  • Nicolaou N, Margadant C, Kevelam SH, Lilien MR, Oosterveld MJ, Kreft M, van Eerde AM, Pfundt R, Terhal PA, van der Zwaag B, Nikkels PG, Sachs N, Goldschmeding R, Knoers NV, Renkema KY, Sonnenberg A (2012) Gain of glycosylation in integrin alpha3 causes lung disease and nephrotic syndrome. J Clin Invest 122:4375–4387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishiuchi R, Murayama O, Fujiwara H, Gu J, Kawakami T, Aimoto S, Wada Y, Sekiguchi K (2003) Characterization of the ligand-binding specificities of integrin alpha3beta1 and alpha6beta1 using a panel of purified laminin isoforms containing distinct alpha chains. J Biochem (Tokyo) 134:497–504

    Article  CAS  PubMed  Google Scholar 

  • Nishiuchi R, Sanzen N, Nada S, Sumida Y, Wada Y, Okada M, Takagi J, Hasegawa H, Sekiguchi K (2005) Potentiation of the ligand-binding activity of integrin alpha3beta1 via association with tetraspanin CD151. Proc Natl Acad Sci U S A 102:1939–1944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishiuchi R, Takagi J, Hayashi M, Ido H, Yagi Y, Sanzen N, Tsuji T, Yamada M, Sekiguchi K (2006) Ligand-binding specificities of laminin-binding integrins: a comprehensive survey of laminin-integrin interactions using recombinant alpha3beta1, alpha6beta1, alpha7beta1 and alpha6beta4 integrins. Matrix Biol 25:189–197

    Article  CAS  PubMed  Google Scholar 

  • Novitskaya V, Romanska H, Kordek R, Potemski P, Kusinska R, Parsons M, Odintsova E, Berditchevski F (2013) Integrin alpha3beta1-CD151 complex regulates dimerization of ErbB2 via RhoA. Oncogene

    Google Scholar 

  • Nowinski D, Lysheden AS, Gardner H, Rubin K, Gerdin B, Ivarsson M (2004) Analysis of gene expression in fibroblasts in response to keratinocyte-derived factors in vitro: potential implications for the wound healing process. J Invest Dermatol 122:216–221

    Article  CAS  PubMed  Google Scholar 

  • Okamoto T, Nakamura A, Hayashi A, Yamaguchi T, Ogawa Y, Natsuga K, Yanagi K, Hotta K (2021) Successful kidney transplantation in a patient with neonatal-onset ILNEB. Pediatr Transpl 25:e13971

    Article  CAS  Google Scholar 

  • Owens DM, Watt FM (2003) Contribution of stem cells and differentiated cells to epidermal tumours. Nat Rev Cancer 3:444–451

    Article  CAS  PubMed  Google Scholar 

  • Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8:221–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paolillo M, Schinelli S (2017) Integrins and exosomes, a dangerous liaison in cancer progression. Cancers 9

    Google Scholar 

  • Peng D, Li PC, Liu T, Zeng HS, Fei YJ, Liu ZX, Zuo HJ (2020) Key role of CD151-integrin complex in lung cancer metastasis and mechanisms involved. Curr Med Sci 40:1148–1155

    Article  CAS  PubMed  Google Scholar 

  • Pesch M, Konig S, Aumailley M (2017) Targeted disruption of the Lama3 gene in adult mice is sufficient to induce skin inflammation and fibrosis. J Invest Dermatol 137:332–340

    Article  CAS  PubMed  Google Scholar 

  • Piipponen M, Li D, Landen NX (2020) The immune functions of keratinocytes in skin wound healing. Int J Mol Sci 21

    Google Scholar 

  • Pilcher BK, Dumin JA, Sudbeck BD, Krane SM, Welgus HG, Parks WC (1997) The activity of collagenase-1 is required for keratinocyte migration on a type I collagen matrix. J Cell Biol 137:1445–1457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piwko-Czuchra A, Koegel H, Meyer H, Bauer M, Werner S, Brakebusch C, Fassler R (2009) Beta1 integrin-mediated adhesion signalling is essential for epidermal progenitor cell expansion. PLoS One 4:e5488

    Article  PubMed  PubMed Central  Google Scholar 

  • Playford MP, Schaller MD (2004) The interplay between Src and integrins in normal and tumor biology. Oncogene 23:7928–7946

    Article  CAS  PubMed  Google Scholar 

  • Poncz M, Eisman R, Heidenreich R, Silver SM, Vilaire G, Surrey S, Schwartz E, Bennett JS (1987) Structure of the platelet membrane glycoprotein IIb. Homology to the alpha subunits of the vitronectin and fibronectin membrane receptors. J Biol Chem 262:8476–8482

    Article  CAS  PubMed  Google Scholar 

  • Pozzi A, Yurchenco PD, Iozzo RV (2017) The nature and biology of basement membranes. Matrix Biol 57-58:1–11

    Article  CAS  PubMed  Google Scholar 

  • Pozzi A, Zent R (2011) Extracellular matrix receptors in branched organs. Curr Opin Cell Biol 23:547–553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pulkkinen L, Christiano AM, Airenne T, Haakana H, Tryggvason K, Uitto J (1994a) Mutations in the gamma 2 chain gene (LAMC2) of kalinin/laminin 5 in the junctional forms of epidermolysis bullosa. Nat Genet 6:293–297

    Article  CAS  PubMed  Google Scholar 

  • Pulkkinen L, Christiano AM, Gerecke D, Wagman DW, Burgeson RE, Pittelkow MR, Uitto J (1994b) A homozygous nonsense mutation in the beta 3 chain gene of laminin 5 (LAMB3) in Herlitz junctional epidermolysis bullosa. Genomics 24:357–360

    Article  CAS  PubMed  Google Scholar 

  • Pulkkinen L, Kimonis VE, Xu Y, Spanou EN, McLean WH, Uitto J (1997) Homozygous alpha6 integrin mutation in junctional epidermolysis bullosa with congenital duodenal atresia. Hum Mol Genet 6:669–674

    Article  CAS  PubMed  Google Scholar 

  • Raghavan S, Bauer C, Mundschau G, Li Q, Fuchs E (2000) Conditional ablation of beta1 integrin in skin. Severe defects in epidermal proliferation, basement membrane formation, and hair follicle invagination. J Cell Biol 150:1149–1160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramovs V, Krotenberg Garcia A, Kreft M, Sonnenberg A (2021) Integrin alpha3beta1 Is a key regulator of several protumorigenic pathways during skin carcinogenesis. J Invest Dermatol 141:732–741 e736

    Article  CAS  PubMed  Google Scholar 

  • Ramovs V, Krotenberg Garcia A, Song JY, de Rink I, Kreft M, Goldschmeding R, Sonnenberg A (2020) Integrin alpha3beta1 in hair bulge stem cells modulates CCN2 expression and promotes skin tumorigenesis. Life Sci Alliance 3

    Google Scholar 

  • Ramovs V, Secades P, Song JY, Thijssen B, Kreft M, Sonnenberg A (2019) Absence of integrin alpha3beta1 promotes the progression of HER2-driven breast cancer in vivo. Breast Cancer Res 21:63

    Article  PubMed  PubMed Central  Google Scholar 

  • Ramovs V, Te Molder L, Sonnenberg A (2017) The opposing roles of laminin-binding integrins in cancer. Matrix Biol 57–58:213–243

    Article  PubMed  Google Scholar 

  • Ranjan A, Bane SM, Kalraiya RD (2014) Glycosylation of the laminin receptor (alpha3beta1) regulates its association with tetraspanin CD151: impssact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. Exp Cell Res 322:249–264

    Article  CAS  PubMed  Google Scholar 

  • Rao Malla R, Gopinath S, Alapati K, Gorantla B, Gondi CS, Rao JS (2013) Knockdown of cathepsin B and uPAR inhibits CD151 and alpha3beta1 integrin-mediated cell adhesion and invasion in glioma. Mol Carcinog 52:777–790

    Article  PubMed  Google Scholar 

  • Raymond K, Cagnet S, Kreft M, Janssen H, Sonnenberg A, Glukhova MA (2011) Control of mammary myoepithelial cell contractile function by alpha3beta1 integrin signalling. EMBO J 30:1896–1906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raymond K, Faraldo MM, Deugnier MA, Glukhova MA (2012) Integrins in mammary development. Semin Cell Develop Biol 23:599–605

    Article  CAS  Google Scholar 

  • Reardon DA, Nabors LB, Stupp R, Mikkelsen T (2008) Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme. Expert Opin Investig Drugs 17:1225–1235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rebustini IT, Patel VN, Stewart JS, Layvey A, Georges-Labouesse E, Miner JH, Hoffman MP (2007) Laminin alpha5 is necessary for submandibular gland epithelial morphogenesis and influences FGFR expression through beta1 integrin signaling. Dev Biol 308:15–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren Y, Hao P, Law SK, Sze SK (2014) Hypoxia-induced changes to integrin alpha 3 glycosylation facilitate invasion in epidermoid carcinoma cell line A431. Mol Cell Proteom: MCP 13:3126–3137

    Article  CAS  PubMed  Google Scholar 

  • Reynolds AR, Hart IR, Watson AR, Welti JC, Silva RG, Robinson SD, Da Violante G, Gourlaouen M, Salih M, Jones MC, Jones DT, Saunders G, Kostourou V, Perron-Sierra F, Norman JC, Tucker GC, Hodivala-Dilke KM (2009) Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors. Nat Med 15:392–400

    Article  CAS  PubMed  Google Scholar 

  • Reynolds LE, Conti FJ, Silva R, Robinson SD, Iyer V, Rudling R, Cross B, Nye E, Hart IR, DiPersio CM, Hodivala-Dilke KM (2008) alpha3beta1 integrin-controlled Smad7 regulates reepithelialization during wound healing in mice. J Clin Invest 118:965–974

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR (2003) Cell migration: integrating signals from front to back. Science 302:1704–1709

    Article  CAS  PubMed  Google Scholar 

  • Romagnoli M, Cagnet S, Chiche A, Bresson L, Baulande S, de la Grange P, De Arcangelis A, Kreft M, Georges-Labouesse E, Sonnenberg A, Deugnier MA, Raymond K, Glukhova MA, Faraldo MM (2019) Deciphering the mammary stem cell niche: a role for laminin-binding integrins. Stem Cell Rep 12:831–844

    Article  CAS  Google Scholar 

  • Ross JA, Webster RG, Lechertier T, Reynolds LE, Turmaine M, Bencze M, Jamshidi Y, Cetin H, Muntoni F, Beeson D, Hodilvala-Dilke K, Conti FJ (2017) Multiple roles of integrin-alpha3 at the neuromuscular junction. J Cell Sci 130:1772–1784

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rousselle P, Aumailley M (1994) Kalinin is more efficient than laminin in promoting adhesion of primary keratinocytes and some other epithelial cells and has a different requirement for integrin receptors. J Cell Biol 125:205–214

    Article  CAS  PubMed  Google Scholar 

  • Rousselle P, Scoazec JY (2020) Laminin 332 in cancer: when the extracellular matrix turns signals from cell anchorage to cell movement. Semin Cancer Biol 62:149–165

    Article  CAS  PubMed  Google Scholar 

  • Ruoslahti E, Pierschbacher MD (1987) New perspectives in cell adhesion: RGD and integrins. Science 238:491–497

    Article  CAS  PubMed  Google Scholar 

  • Ryan MC, Lee K, Miyashita Y, Carter WG (1999) Targeted disruption of the LAMA3 gene in mice reveals abnormalities in survival and late stage differentiation of epithelial cells. J Cell Biol 145:1309–1323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sachs N, Claessen N, Aten J, Kreft M, Teske GJ, Koeman A, Zuurbier CJ, Janssen H, Sonnenberg A (2012a) Blood pressure influences end-stage renal disease of Cd151 knockout mice. J Clin Invest 122:348–358

    Article  CAS  PubMed  Google Scholar 

  • Sachs N, Kreft M, van den Bergh Weerman MA, Beynon AJ, Peters TA, Weening JJ, Sonnenberg A (2006) Kidney failure in mice lacking the tetraspanin CD151. J Cell Biol 175:33–39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sachs N, Secades P, van Hulst L, Kreft M, Song JY, Sonnenberg A (2012b) Loss of integrin alpha3 prevents skin tumor formation by promoting epidermal turnover and depletion of slow-cycling cells. Proc Natl Acad Sci U S A 109:21468–21473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sachs N, Secades P, van Hulst L, Song JY, Sonnenberg A (2014) Reduced susceptibility to two-stage skin carcinogenesis in mice with epidermis-specific deletion of CD151. J Invest Dermatol 134:221–228

    Article  CAS  PubMed  Google Scholar 

  • Sadej R, Romanska H, Baldwin G, Gkirtzimanaki K, Novitskaya V, Filer AD, Krcova Z, Kusinska R, Ehrmann J, Buckley CD, Kordek R, Potemski P, Eliopoulos AG, Lalaniel N, Berditchevski F (2009) CD151 regulates tumorigenesis by modulating the communication between tumor cells and endothelium. Mol Cancer Res 7:787–798

    Article  CAS  PubMed  Google Scholar 

  • Sadej R, Romanska H, Kavanagh D, Baldwin G, Takahashi T, Kalia N, Berditchevski F (2010) Tetraspanin CD151 regulates transforming growth factor beta signaling: implication in tumor metastasis. Cancer Res 70:6059–6070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saito Y, Sekine W, Sano R, Komatsu S, Mizuno H, Katabami K, Shimada K, Oku T, Tsuji T (2010) Potentiation of cell invasion and matrix metalloproteinase production by alpha3beta1 integrin-mediated adhesion of gastric carcinoma cells to laminin-5. Clin Exp Metastasis 27:197–205

    Article  CAS  PubMed  Google Scholar 

  • Saravanan C, Liu FT, Gipson IK, Panjwani N (2009) Galectin-3 promotes lamellipodia formation in epithelial cells by interacting with complex N-glycans on alpha3beta1 integrin. J Cell Sci 122:3684–3693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarker FA, Prior VG, Bax S, O’Neill GM (2020) Forcing a growth factor response – tissue-stiffness modulation of integrin signaling and crosstalk with growth factor receptors. J Cell Sci 133

    Google Scholar 

  • Sasaki T, Gohring W, Mann K, Brakebusch C, Yamada Y, Fassler R, Timpl R (2001) Short arm region of laminin-5 gamma2 chain: structure, mechanism of processing and binding to heparin and proteins. J Mol Biol 314:751–763

    Article  CAS  PubMed  Google Scholar 

  • Scales TM, Jayo A, Obara B, Holt MR, Hotchin NA, Berditchevski F, Parsons M (2013) alpha3beta1 integrins regulate CD151 complex assembly and membrane dynamics in carcinoma cells within 3D environments. Oncogene 32:3965–3979

    Article  CAS  PubMed  Google Scholar 

  • Schafer M, Werner S (2008) Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 9:628–638

    Article  CAS  PubMed  Google Scholar 

  • Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez JR, Zhou D, Kreger BT, Vasioukhin V, Avruch J, Brummelkamp TR, Camargo FD (2011) Yap1 acts downstream of alpha-catenin to control epidermal proliferation. Cell 144:782–795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schnittert J, Bansal R, Storm G, Prakash J (2018) Integrins in wound healing, fibrosis and tumor stroma: high potential targets for therapeutics and drug delivery. Adv Drug Deliv Rev 129:37–53

    Article  CAS  PubMed  Google Scholar 

  • Schwartz MA, Ginsberg MH (2002) Networks and crosstalk: integrin signalling spreads. Nat Cell Biol 4:E65–E68

    Article  CAS  PubMed  Google Scholar 

  • Sehgal BU, DeBiase PJ, Matzno S, Chew TL, Claiborne JN, Hopkinson SB, Russell A, Marinkovich MP, Jones JC (2006) Integrin beta4 regulates migratory behavior of keratinocytes by determining laminin-332 organization. J Biol Chem 281:35487–35498

    Article  CAS  PubMed  Google Scholar 

  • Seo DW, Li H, Guedez L, Wingfield PT, Diaz T, Salloum R, Wei BY, Stetler-Stevenson WG (2003) TIMP-2 mediated inhibition of angiogenesis: an MMP-independent mechanism. Cell 114:171–180

    Article  CAS  PubMed  Google Scholar 

  • Shang M, Koshikawa N, Schenk S, Quaranta V (2001) The LG3 module of laminin-5 harbors a binding site for integrin α3β1 that promotes cell adhesion, spreading and migration. J Biol Chem 276:33045–33053

    Article  CAS  PubMed  Google Scholar 

  • Shi Z, Liu Y, Johnson JJ, Stack MS (2011) Urinary-type plasminogen activator receptor (uPAR) modulates oral cancer cell behavior with alteration in p130cas. Mol Cell Biochem 357:151–161

    Article  CAS  PubMed  Google Scholar 

  • Shukrun R, Vivante A, Pleniceanu O, Vax E, Anikster Y, Dekel B, Lotan D (2014) A human integrin-alpha3 mutation confers major renal developmental defects. PLoS One 9:e90879

    Article  PubMed  PubMed Central  Google Scholar 

  • Singer AJ, Clark RA (1999) Cutaneous wound healing. N Engl J Med 341:738–746

    Article  CAS  PubMed  Google Scholar 

  • Singh A, Fedele C, Lu H, Nevalainen MT, Keen JH, Languino LR (2016) Exosome-mediated transfer of alphavbeta3 integrin from tumorigenic to nontumorigenic cells promotes a migratory phenotype. Mol Cancer Res 14:1136–1146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh P, Chen C, Pal-Ghosh S, Stepp MA, Sheppard D, Van De Water L (2009) Loss of integrin alpha9beta1 results in defects in proliferation, causing poor re-epithelialization during cutaneous wound healing. J Invest Dermatol 129:217–228

    Article  CAS  PubMed  Google Scholar 

  • Singh P, Reimer CL, Peters JH, Stepp MA, Hynes RO, Van De Water L (2004) The spatial and temporal expression patterns of integrin alpha9beta1 and one of its ligands, the EIIIA segment of fibronectin, in cutaneous wound healing. J Invest Dermatol 123:1176–1181

    Article  CAS  PubMed  Google Scholar 

  • Sroka TC, Pennington ME, Cress AE (2006) Synthetic D-amino acid peptide inhibits tumor cell motility on laminin-5. Carcinogenesis 27:1748–1757

    Article  CAS  PubMed  Google Scholar 

  • Stanco A, Szekeres C, Patel N, Rao S, Campbell K, Kreidberg JA, Polleux F, Anton ES (2009) Netrin-1-alpha3beta1 integrin interactions regulate the migration of interneurons through the cortical marginal zone. Proc Natl Acad Sci U S A 106:7595–7600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stipp CS (2010) Laminin-binding integrins and their tetraspanin partners as potential antimetastatic targets. Expert Rev Mol Med 12:e3

    Article  PubMed  PubMed Central  Google Scholar 

  • Stupp R, Ruegg C (2007) Integrin inhibitors reaching the clinic. J Clin Oncol 25:1637–1638

    Article  CAS  PubMed  Google Scholar 

  • Subbaram S, DiPersio CM (2011) Integrin alpha3beta1 as a breast cancer target. Expert Opin Ther Targets 15:1197–1210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Subbaram S, Kuentzel M, Frank D, DiPersio CM, Chittur SV (2010) Determination of alternate splicing events using the Affymetrix Exon 1.0 ST arrays. Methods Mol Biol 632:63–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Subbaram S, Lyons SP, Svenson KB, Hammond SL, McCabe LG, Chittur SV, DiPersio CM (2014) Integrin alpha3beta1 controls mRNA splicing that determines Cox-2 mRNA stability in breast cancer cells. J Cell Sci 127:1179–1189

    CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki S, Argraves WS, Arai H, Languino LR, Pierschbacher MD, Ruoslahti E (1987) Amino acid sequence of the vitronectin receptor alpha subunit and comparative expression of adhesion receptor mRNAs. J Biol Chem 262:14080–14085

    Article  CAS  PubMed  Google Scholar 

  • Taddei I, Deugnier MA, Faraldo MM, Petit V, Bouvard D, Medina D, Fassler R, Thiery JP, Glukhova MA (2008) Beta1 integrin deletion from the basal compartment of the mammary epithelium affects stem cells. Nat Cell Biol 10:716–722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takada Y, Murphy E, Pil P, Chen C, Ginsberg MH, Hemler ME (1991) Molecular cloning and expression of the cDNA for a3 subunit of human α3β1 (VLA-3), an integrin receptor for fibronectin, laminin, and collagen. J Cell Biol 115:257–266

    Article  CAS  PubMed  Google Scholar 

  • Takada Y, Wayner EA, Carter WG, Hemler ME (1988) Extracellular matrix receptors, ECMRII and ECMRI, for collagen and fibronectin correspond to VLA-2 and VLA-3 in the VLA family of heterodimers. J Cell Biochem 37:385–393

    Article  CAS  PubMed  Google Scholar 

  • Takada Y, Ylanne J, Mandelman D, Puzon W, Ginsberg MH (1992) A point mutation of integrin beta 1 subunit blocks binding of alpha 5 beta 1 to fibronectin and invasin but not recruitment to adhesion plaques. J Cell Biol 119:913–921

    Article  CAS  PubMed  Google Scholar 

  • Takatsuki H, Komatsu S, Sano R, Takada Y, Tsuji T (2004) Adhesion of gastric carcinoma cells to peritoneum mediated by alpha3beta1 integrin (VLA-3). Cancer Res 64:6065–6070

    Article  CAS  PubMed  Google Scholar 

  • Takizawa Y, Shimizu H, Nishikawa T, Hatta N, Pulkkinen L, Uitto J (1997) Novel ITGB4 mutations in a patient with junctional epidermolysis bullosa-pyloric atresia syndrome and altered basement membrane zone immunofluorescence for the alpha6beta4 integrin. J Invest Dermatol 108:943–946

    Article  CAS  PubMed  Google Scholar 

  • Tamkun JW, DeSimone DW, Fonda D, Patel RS, Buck C, Horwitz AF, Hynes RO (1986) Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell 42:271–282

    Article  Google Scholar 

  • Tamura RN, Cooper HM, Collo G, Quaranta V (1991) Cell type-specific integrin variants with alternative a chain cytoplasmic domains. Proc Natl Acad Sci U S A 88:10183–10187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tayem R, Niemann C, Pesch M, Morgner J, Niessen CM, Wickstrom SA, Aumailley M (2021) Laminin 332 is indispensable for homeostatic epidermal differentiation programs. J Invest Dermatol 141:2602–2610 e2603

    Article  CAS  PubMed  Google Scholar 

  • Te Molder L, Juksar J, Harkes R, Wang W, Kreft M, Sonnenberg A (2019) Tetraspanin CD151 and integrin alpha3beta1 contribute to the stabilization of integrin alpha6beta4-containing cell-matrix adhesions. J Cell Sci 132

    Google Scholar 

  • Thiemann RF, Nelson DA, DiPersio CM, Larsen M, LaFlamme SE (2019) Establishment of a murine pro-acinar cell line to characterize roles for FGF2 and alpha3beta1 integrins in regulating pro-acinar characteristics. Scientific Rep 9:10984

    Article  Google Scholar 

  • Thompson BJ (2020) YAP/TAZ: drivers of tumor growth, metastasis, and resistance to therapy. BioEssays 42:e1900162

    Article  PubMed  Google Scholar 

  • Tsubota Y, Mizushima H, Hirosaki T, Higashi S, Yasumitsu H, Miyazaki K (2000) Isolation and activity of proteolytic fragment of laminin-5 alpha3 chain. Biochem Biophys Res Commun 278:614–620

    Article  CAS  PubMed  Google Scholar 

  • Tsuji T (2004) Physiological and pathological roles of alpha3beta1 integrin. J Membr Biol 200:115–132

    Article  CAS  PubMed  Google Scholar 

  • Tsuji T, Yamamoto F, Miura Y, Takio K, Titani K, Pawar S, Osawa T, Hakomori S (1990) Characterization through cDNA cloning of galactoprotein b3 (Gap b3), a cell surface membrane glycoprotein showing enhanced expression on oncogenic transformation. Identification of Gap b3 as a member of the integrin superfamily. J Biol Chem 265:7016–7021

    Article  CAS  PubMed  Google Scholar 

  • Utani A, Nomizu M, Yamada Y (1997) Fibulin-2 binds to the short arms of laminin-5 and laminin-1 via conserved amino acid sequences. J Biol Chem 272:2814–2820

    Article  CAS  PubMed  Google Scholar 

  • Vahidnezhad H, Youssefian L, Saeidian AH, Mahmoudi H, Touati A, Abiri M, Kajbafzadeh AM, Aristodemou S, Liu L, McGrath JA, Ertel A, Londin E, Kariminejad A, Zeinali S, Fortina P, Uitto J (2018) Recessive mutation in tetraspanin CD151 causes Kindler syndrome-like epidermolysis bullosa with multi-systemic manifestations including nephropathy. Matrix Biol 66:22–33

    Article  CAS  PubMed  Google Scholar 

  • van der Neut R, Krimpenfort P, Calafat J, Niessen CM, Sonnenberg A (1996) Epithelial detachment due to absence of hemidesmosomes in integrin beta 4 null mice. Nat Genet 13:366–369

    Article  PubMed  Google Scholar 

  • Varelas X (2014) The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease. Development 141:1614–1626

    Article  CAS  PubMed  Google Scholar 

  • Varney SD, Wu L, Longmate WM, DiPersio CM, Van De Water L (2021) Loss of integrin alpha9beta1 on tumor keratinocytes enhances the stromal vasculature and growth of cutaneous tumors. J Invest, Dermatol

    Google Scholar 

  • Varzavand A, Drake JM, Svensson RU, Herndon ME, Zhou B, Henry MD, Stipp CS (2013) Integrin alpha3beta1 regulates tumor cell responses to stromal cells and can function to suppress prostate cancer metastatic colonization. Clin Exp Metastasis 30:541–552

    Article  CAS  PubMed  Google Scholar 

  • Varzavand A, Hacker W, Ma D, Gibson-Corley K, Hawayek M, Tayh OJ, Brown JA, Henry MD, Stipp CS (2016) alpha3beta1 integrin suppresses prostate cancer metastasis via regulation of the hippo pathway. Cancer Res

    Google Scholar 

  • Veitch DP, Nokelainen P, McGowan KA, Nguyen TT, Nguyen NE, Stephenson R, Pappano WN, Keene DR, Spong SM, Greenspan DS, Findell PR, Marinkovich MP (2003) Mammalian tolloid metalloproteinase, and not matrix metalloprotease 2 or membrane type 1 metalloprotease, processes laminin-5 in keratinocytes and skin. J Biol Chem 278:15661–15668

    Article  CAS  PubMed  Google Scholar 

  • Vlahakis NE, Young BA, Atakilit A, Hawkridge AE, Issaka RB, Boudreau N, Sheppard D (2007) Integrin alpha9beta1 directly binds to vascular endothelial growth factor (VEGF)-A and contributes to VEGF-A-induced angiogenesis. J Biol Chem 282:15187–15196

    Article  CAS  PubMed  Google Scholar 

  • Wali VB, Haskins JW, Gilmore-Hebert M, Platt JT, Liu Z, Stern DF (2014) Convergent and divergent cellular responses by ErbB4 isoforms in mammary epithelial cells. Mol Cancer Res 12:1140–1155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Fu W, Im JH, Zhou Z, Santoro SA, Iyer V, DiPersio CM, Yu QC, Quaranta V, Al-Mehdi A, Muschel RJ (2004) Tumor cell {alpha}3{beta}1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis. J Cell Biol 164:935–941

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, ** H, Rapraeger AC (2015) Syndecan-1 and Syndecan-4 capture epidermal growth factor receptor family members and the alpha3beta1 integrin via binding sites in their ectodomains: novel synstatins prevent kinase capture and inhibit alpha6beta4-integrin-dependent epithelial cell motility. J Biol Chem 290:26103–26113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Z, Chui WK, Ho PC (2010) Integrin targeted drug and gene delivery. Expert Opin Drug Deliv 7:159–171

    Article  CAS  PubMed  Google Scholar 

  • Warren JSA, **ao Y, Lamar JM (2018) YAP/TAZ activation as a target for treating metastatic cancer. Cancers 10

    Google Scholar 

  • Watt FM (2002) Role of integrins in regulating epidermal adhesion, growth and differentiation. EMBO J 21:3919–3926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wayner EA, Carter WG (1987) Identification of multiple cell adhesion receptors for collagen and fibronectin in human fibrosarcoma cells possessing unique a and common b subunits. J Cell Biol 105:1873–1884

    Article  CAS  PubMed  Google Scholar 

  • Wayner EA, Carter WG, Piotrowicz RS, Kunicki TJ (1988) The function of multiple extracellular matrix receptors in mediating cell adhesion to extracellular matrix: preparation of monoclonal antibodies to the fibronectin receptor that specifically inhibit cell adhesion to fibronectin and react with platelet glycoproteins Ic-IIa. J Cell Biol 107:1881–1891

    Article  CAS  PubMed  Google Scholar 

  • Wayner EA, Gil SG, Murphy GF, Wilke MS, Carter WG (1993) Epiligrin, a component of epithelial basement membranes, is an adhesive ligand for alpha 3 beta 1 positive T lymphocytes. J Cell Biol 121:1141–1152

    Article  CAS  PubMed  Google Scholar 

  • Wei Y, Eble JA, Wang Z, Kreidberg JA, Chapman HA (2001) Urokinase receptors promote beta1 integrin function through interactions with integrin alpha3beta1. Mol Biol Cell 12:2975–2986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weitzman JB, Pasqualini R, Takada Y, Hemler ME (1993) The function and distinctive regulation of the integrin VLA-3 in cell adhesion, spreading, and homotypic cell aggregation. J Biol Chem 268:8651–8657

    Article  CAS  PubMed  Google Scholar 

  • Weller M, Nabors LB, Gorlia T, Leske H, Rushing E, Bady P, Hicking C, Perry J, Hong YK, Roth P, Wick W, Goodman SL, Hegi ME, Picard M, Moch H, Straub J, Stupp R (2016) Cilengitide in newly diagnosed glioblastoma: biomarker expression and outcome. Oncotarget 7:15018–15032

    Article  PubMed  PubMed Central  Google Scholar 

  • Werner S, Krieg T, Smola H (2007) Keratinocyte-fibroblast interactions in wound healing. J Invest Dermatol 127:998–1008

    Article  CAS  PubMed  Google Scholar 

  • Winograd-Katz SE, Fassler R, Geiger B, Legate KR (2014) The integrin adhesome: from genes and proteins to human disease. Nat Rev Mol Cell Biol 15:273–288

    Article  CAS  PubMed  Google Scholar 

  • Winterwood NE, Varzavand A, Meland MN, Ashman LK, Stipp CS (2006) A critical role for tetraspanin CD151 in alpha3beta1 and alpha6beta4 integrin-dependent tumor cell functions on laminin-5. Mol Biol Cell 17:2707–2721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wright MD, Geary SM, Fitter S, Moseley GW, Lau LM, Sheng KC, Apostolopoulos V, Stanley EG, Jackson DE, Ashman LK (2004) Characterization of mice lacking the tetraspanin superfamily member CD151. Mol Cell Biol 24:5978–5988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu PH, Opadele AE, Onodera Y, Nam JM (2019) Targeting integrins in cancer nanomedicine: applications in cancer diagnosis and therapy. Cancers 11

    Google Scholar 

  • **ao W, Li T, Bononi FC, Lac D, Kekessie IA, Liu Y, Sanchez E, Mazloom A, Ma AH, Lin J, Tran J, Yang K, Lam KS, Liu R (2016) Discovery and characterization of a high-affinity and high-specificity peptide ligand LXY30 for in vivo targeting of alpha3 integrin-expressing human tumors. EJNMMI Res 6:18

    Article  PubMed  PubMed Central  Google Scholar 

  • **ao W, Ma W, Wei S, Li Q, Liu R, Carney RP, Yang K, Lee J, Nyugen A, Yoneda KY, Lam KS, Li T (2019) High-affinity peptide ligand LXY30 for targeting alpha3beta1 integrin in non-small cell lung cancer. J Hematol Oncol 12:56

    Article  PubMed  PubMed Central  Google Scholar 

  • Yalcin EG, He Y, Orhan D, Pazzagli C, Emiralioglu N, Has C (2015) Crucial role of posttranslational modifications of integrin alpha3 in interstitial lung disease and nephrotic syndrome. Hum Mol Genet 24:3679–3688

    CAS  PubMed  Google Scholar 

  • Yanez-Mo M, Alfranca A, Cabanas C, Marazuela M, Tejedor R, Ursa MA, Ashman LK, de Landazuri MO, Sanchez-Madrid F (1998) Regulation of endothelial cell motility by complexes of tetraspan molecules CD81/TAPA-1 and CD151/PETA-3 with alpha3 beta1 integrin localized at endothelial lateral junctions. J Cell Biol 141:791–804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yauch RL, Berditchevsky F, Harler MB, Reichner J, Hemler ME (1998) Highly stoichiometric, stable, and specific association of integrin α3β1 with CD151 provides a major link to phosphatidylinositol 4-kinase, and may regulate cell migration. Mol Biol Cell 9:2751–2765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yauch RL, Kazarov AR, Desai B, Lee RT, Hemler ME (2000) Direct extracellular contact between integrin α3β1 and TM4SF protein CD151. JBiolChem 275:9230–9238

    CAS  Google Scholar 

  • Yazlovitskaya EM, Plosa E, Bock F, Viquez OM, Mernaugh G, Gewin LS, De Arcangelis A, Georges-Labouesse E, Sonnenberg A, Blackwell TS, Pozzi A, Zent R (2021) The laminin-binding integrins regulate nuclear factor kappa-beta-dependent epithelial cell polarity and inflammation. J Cell Sci

    Google Scholar 

  • Yazlovitskaya EM, Tseng HY, Viquez O, Tu T, Mernaugh G, McKee KK, Riggins K, Quaranta V, Pathak A, Carter BD, Yurchenco P, Sonnenberg A, Bottcher RT, Pozzi A, Zent R (2015) Integrin alpha3beta1 regulates kidney collecting duct development via TRAF6-dependent K63-linked polyubiquitination of Akt. Mol Biol Cell 26:1857–1874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan Y, Jiang YC, Sun CK, Chen QM (2016) Role of the tumor microenvironment in tumor progression and the clinical applications (Review). Oncol Rep 35:2499–2515

    Article  CAS  PubMed  Google Scholar 

  • Zevian SC, Johnson JL, Winterwood NE, Walters KS, Herndon ME, Henry MD, Stipp CS (2015) CD151 promotes alpha3beta1 integrin-dependent organization of carcinoma cell junctions and restrains collective cell invasion. Cancer Biol Ther 16:1626–1640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang F, Tom CC, Kugler MC, Ching TT, Kreidberg JA, Wei Y, Chapman HA (2003) Distinct ligand binding sites in integrin alpha3beta1 regulate matrix adhesion and cell-cell contact. J Cell Biol 163:177–188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Liu J (2013) Tumor stroma as targets for cancer therapy. Pharmacol Ther 137:200–215

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Wu Y, Yin X, Zhu Z, Rojalin T, **ao W, Zhang D, Huang Y, Li L, Baehr CM, Yu X, Ajena Y, Li Y, Wang L, Lam KS (2021) Tumor receptor-mediated in vivo modulation of the morphology, phototherapeutic properties, and pharmacokinetics of smart nanomaterials. ACS Nano 15:468–479

    Article  CAS  PubMed  Google Scholar 

  • Zhang XP, Puzon-McLaughlin W, Irie A, Kovach N, Prokopishyn NL, Laferte S, Takeuchi K, Tsuji T, Takada Y (1999) Alpha 3 beta 1 adhesion to laminin-5 and invasin: critical and differential role of integrin residues clustered at the boundary between alpha 3 N-terminal repeats 2 and 3. Biochemistry 38:14424–14431

    Article  CAS  PubMed  Google Scholar 

  • Zhao B, Li L, Tumaneng K, Wang CY, Guan KL (2010) A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP). Genes Dev 24:72–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng R, Longmate WM, DeFreest L, Varney S, Wu L, DiPersio CM, Van De Water L (2019) Keratinocyte integrin alpha3beta1 promotes secretion of IL-1alpha to effect paracrine regulation of fibroblast gene expression and differentiation. J Invest, Dermatol

    Google Scholar 

  • Zheng R, Varney SD, Wu L, DiPersio CM, Van De Water L (2021) Integrin alpha4beta1 is required for IL-1alpha- and Nrf2-dependent, Cox-2 induction in fibroblasts, supporting a mechanism that suppresses alpha-SMA expression. Wound Repair Regen 29:597–601

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou B, Gibson-Corley KN, Herndon ME, Sun Y, Gustafson-Wagner E, Teoh-Fitzgerald M, Domann FE, Henry MD, Stipp CS (2014) Integrin alpha3beta1 can function to promote spontaneous metastasis and lung colonization of invasive breast carcinoma. Mol Cancer Res 12:143–154

    Article  CAS  PubMed  Google Scholar 

  • Zhu AJ, Haase I, Watt FM (1999) Signaling via beta1 integrins and mitogen-activated protein kinase determines human epidermal stem cell fate in vitro. Proc Natl Acad Sci U S A 96:6728–6733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zuidema A, Wang W, Sonnenberg A (2020) Crosstalk between cell adhesion complexes in regulation of mechanotransduction. BioEssays 42:e2000119

    Article  PubMed  Google Scholar 

  • Zweers MC, Davidson JM, Pozzi A, Hallinger R, Janz K, Quondamatteo F, Leutgeb B, Krieg T, Eckes B (2007) Integrin alpha2beta1 is required for regulation of murine wound angiogenesis but is dispensable for reepithelialization. J Invest Dermatol 127:467–478

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Drs. Arnoud Sonnenberg, John Lamar, Susan LaFlamme, Livingston Van De Water, and Johannes A. Eble for critical reading of the manuscript, and to colleagues at Albany Medical College and members of the DiPersio laboratory for valuable discussions and insights. We offer our apologies to the many researchers whose valuable contributions to the field could not be cited here due to space constraints, but which are covered in other reviews that we have referenced.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C. Michael DiPersio .

Editor information

Editors and Affiliations

Ethics declarations

The authors declare no competing financial interests or other conflicts of interest. Research in the DiPersio laboratory is supported by NIH grants from NCI (R01CA129637) and NIAMS (R01AR063778). Investigations described in this chapter involving animals or humans were conducted in compliance with corresponding ethical guidelines, and informed consent was obtained in cases where humans were involved.

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

DiPersio, C.M., Longmate, W.M. (2023). Roles for Integrin α3β1 in Development and Disease. In: Gullberg, D., Eble, J.A. (eds) Integrins in Health and Disease. Biology of Extracellular Matrix, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-031-23781-2_2

Download citation

Publish with us

Policies and ethics

Navigation