Abstract
Autotaxin has emerged as a prominent and critical element in biological processes involving the lipid signaling molecule lysophosphatidic acid (LPA). Such processes are mediated largely by LPA’s cognate G protein-coupled receptors, and they are related to a widespread array of physiological and pathophysiological actions. Autotaxin itself was originally identified as a tumor cell motility-stimulating factor and then found to be highly expressed by a large variety of tumor cells. Thus, it has received much attention in cancer biology prompting extensive research toward a better understanding of its enzymatic LPA generating activity shown to drive tumorigenesis and tumor cell invasion. More recently, however, diverse roles of autotaxin have become apparent including regulatory functions in stem cell biology and neurodevelopment. In addition, there is increasing evidence for non-catalytic functions of autotaxin. This chapter will introduce, from a historical perspective, the major characteristics of autotaxin, and it will define autotaxin’s main structure–function relationships. Importantly, it will review autotaxin’s evolving roles in stem cell biology and neurodevelopment.
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Abbreviations
- ATX:
-
Autotaxin
- CNS:
-
Central nervous system
- ENPP2:
-
Ecto-nucleotide pyrophosphatase/phosphodiesterase 2
- LPA:
-
Lysophosphatidic acid
- LPC:
-
Lysophosphatidylcholine
- LysoLPD:
-
Lysophospholipase D
- MORFO:
-
Modulator of oligodendrocyte differentiation and focal adhesion organization
- PD-Iα:
-
Phosphodiesterase Iα
References
Stracke ML, Krutzsch HC, Unsworth EJ, Arestad A, Cioce V, Schiffmann E, Liotta LA (1992) Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J Biol Chem 267(4):2524–2529
Moolenaar WH (2002) Lysophospholipids in the limelight: autotaxin takes center stage. J Cell Biol 158(2):197–199
Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, Yasuda K, Fukuzawa K (2002) Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem 277(42):39436–39442
Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, Yamori T, Mills GB, Inoue K, Aoki J, Arai H (2002) Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Biol 158(2):227–233
Ferry G, Tellier E, Try A, Gres S, Naime I, Simon MF, Rodriguez M, Boucher J, Tack I, Gesta S, Chomarat P, Dieu M, Raes M, Galizzi JP, Valet P, Boutin JA, Saulnier-Blache JS (2003) Autotaxin is released from adipocytes, catalyzes lysophosphatidic acid synthesis, and activates preadipocyte proliferation. Up-regulated expression with adipocyte differentiation and obesity. J Biol Chem 278(20):18162–18169
Giganti A, Rodriguez M, Fould B, Moulharat N, Coge F, Chomarat P, Galizzi JP, Valet P, Saulnier-Blache JS, Boutin JA, Ferry G (2008) Murine and human autotaxin alpha, beta, and gamma isoforms: gene organization, tissue distribution, and biochemical characterization. J Biol Chem 283(12):7776–7789
Hashimoto T, Okudaira S, Igarashi K, Hama K, Yatomi Y, Aoki J (2012) Identification and biochemical characterization of a novel autotaxin isoform, ATXdelta, with a four-amino acid deletion. J Biochem 151(1):89–97
Federico L, Jeong KJ, Vellano CP, Mills GB (2016) Autotaxin, a lysophospholipase D with pleomorphic effects in oncogenesis and cancer progression. J Lipid Res 57(1):25–35
Narita M, Goji J, Nakamura H, Sano K (1994) Molecular cloning, expression, and localization of a brain-specific phosphodiesterase I/nucleotide pyrophosphatase (PD-I alpha) from rat brain. J Biol Chem 269(45):28235–28242
Fuss B, Baba H, Phan T, Tuohy VK, Macklin WB (1997) Phosphodiesterase I, a novel adhesion molecule and/or cytokine involved in oligodendrocyte function. J Neurosci 17(23):9095–9103
Houben AJ, van Wijk XM, van Meeteren LA, van Zeijl L, van de Westerlo EM, Hausmann J, Fish A, Perrakis A, van Kuppevelt TH, Moolenaar WH (2013) The polybasic insertion in autotaxin alpha confers specific binding to heparin and cell surface heparan sulfate proteoglycans. J Biol Chem 288(1):510–519
Kawagoe H, Soma O, Goji J, Nishimura N, Narita M, Inazawa J, Nakamura H, Sano K (1995) Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2). Genomics 30(2):380–384
Lee HY, Clair T, Mulvaney PT, Woodhouse EC, Aznavoorian S, Liotta LA, Stracke ML (1996) Stimulation of tumor cell motility linked to phosphodiesterase catalytic site of autotaxin. J Biol Chem 271(40):24408–24412
Bachner D, Ahrens M, Betat N, Schroder D, Gross G (1999) Developmental expression analysis of murine autotaxin (ATX). Mech Dev 84(1–2):121–125
Ohuchi H, Hayashibara Y, Matsuda H, Onoi M, Mitsumori M, Tanaka M, Aoki J, Arai H, Noji S (2007) Diversified expression patterns of autotaxin, a gene for phospholipid-generating enzyme during mouse and chicken development. Dev Dyn 236(4):114–1143
Savaskan NE, Rocha L, Kotter MR, Baer A, Lubec G, van Meeteren LA, Kishi Y, Aoki J, Moolenaar WH, Nitsch R, Brauer AU (2006) Autotaxin (NPP-2) in the brain: cell type-specific expression and regulation during development and after neurotrauma. Cell Mol Life Sci 64(2):230–243
Sato K, Malchinkhuu E, Muraki T, Ishikawa K, Hayashi K, Tosaka M, Mochiduki A, Inoue K, Tomura H, Mogi C, Nochi H, Tamoto K, Okajima F (2005) Identification of autotaxin as a neurite retraction-inducing factor of PC12 cells in cerebrospinal fluid and its possible sources. J Neurochem 92(4):904–914
Murata J, Lee HY, Clair T, Krutzsch HC, Arestad AA, Sobel ME, Liotta LA, Stracke ML (1994) cDNA cloning of the human tumor motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases. J Biol Chem 269(48):30479–30484
Stracke ML, Clair T, Liotta LA (1997) Autotaxin, tumor motility-stimulating exophosphodiesterase. Adv Enzyme Regul 37:135–144
Clair T, Lee HY, Liotta LA, Stracke ML (1997) Autotaxin is an exoenzyme possessing 5’-nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities. J Biol Chem 272(2):996–1001
Deissler H, Lottspeich F, Rajewsky MF (1995) Affinity purification and cDNA cloning of rat neural differentiation and tumor cell surface antigen gp130RB13-6 reveals relationship to human and murine PC-1. J Biol Chem 270(17):9849–9855
**-Hua P, Goding JW, Nakamura H, Sano K (1997) Molecular cloning and chromosomal localization of PD-Ibeta (PDNP3), a new member of the human phosphodiesterase I genes. Genomics 45(2):412–415
Bollen M, Gijsbers R, Ceulemans H, Stalmans W, Stefan C (2000) Nucleotide pyrophosphatases/phosphodiesterases on the move. Crit Rev Biochem Mol Biol 35(6):393–432
Zimmermann H, Beaudoin AR, Bollen M, Goding JW, Guidotti G, Kirley TL, Robson SC, Sano K (2000) Proposed nomenclature for two novel nucleotide hydrolyzing enzyme families expressed on the cell surface. In: Vanduffel L, Lemmens R (eds) Ecto-ATPases and related ectonucleotidases. Shaker Publishing B.V, Maastrich, pp 1–8
Stefan C, Jansen S, Bollen M (2005) NPP-type ectophosphodiesterases: unity in diversity. Trends Biochem Sci 30(10):542–550
Gijsbers R, Aoki J, Arai H, Bollen M (2003) The hydrolysis of lysophospholipids and nucleotides by autotaxin (NPP2) involves a single catalytic site. FEBS Lett 538(1–3):60–64
van Meeteren LA, Ruurs P, Stortelers C, Bouwman P, van Rooijen MA, Pradere JP, Pettit TR, Wakelam MJ, Saulnier-Blache JS, Mummery CL, Moolenaar WH, Jonkers J (2006) Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol Cell Biol 26(13):5015–5022
Kishi Y, Okudaira S, Tanaka M, Hama K, Shida D, Kitayama J, Yamori T, Aoki J, Fujimaki T, Arai H (2006) Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine to lysophosphatidic acid. J Biol Chem 281(25):17492–17500
Hama K, Aoki J, Fukaya M, Kishi Y, Sakai T, Suzuki R, Ohta H, Yamori T, Watanabe M, Chun J, Arai H (2004) Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1. J Biol Chem 279(17):17634–17639
Gaetano CG, Samadi N, Tomsig JL, Macdonald TL, Lynch KR, Brindley DN (2009) Inhibition of autotaxin production or activity blocks lysophosphatidylcholine-induced migration of human breast cancer and melanoma cells. Mol Carcinog 48(9):801–809
Tanaka M, Okudaira S, Kishi Y, Ohkawa R, Iseki S, Ota M, Noji S, Yatomi Y, Aoki J, Arai H (2006) Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid. J Biol Chem 281(35):25822–25830
Yukiura H, Kano K, Kise R, Inoue A, Aoki J (2015) Autotaxin overexpression causes embryonic lethality and vascular defects. PLoS One 10(5):e0126734
Clair T, Aoki J, Koh E, Bandle RW, Nam SW, Ptaszynska MM, Mills GB, Schiffmann E, Liotta LA, Stracke ML (2003) Autotaxin hydrolyzes sphingosylphosphorylcholine to produce the regulator of migration, sphingosine-1-phosphate. Cancer Res 63(17):5446–5453
Tsuda S, Okudaira S, Moriya-Ito K, Shimamoto C, Tanaka M, Aoki J, Arai H, Murakami-Murofushi K, Kobayashi T (2006) Cyclic phosphatidic acid is produced by autotaxin in blood. J Biol Chem 281(36):26081–26088
Parrill AL, Baker DL (2008) Autotaxin inhibition: challenges and progress toward novel anti-cancer agents. Anticancer Agents Med Chem 8(8):917–923
Xu X, Yang G, Zhang H, Prestwich GD (2009) Evaluating dual activity LPA receptor pan-antagonist/autotaxin inhibitors as anti-cancer agents in vivo using engineered human tumors. Prostaglandins Other Lipid Mediat 89(3–4):140–146
Gotoh M, Fujiwara Y, Yue J, Liu J, Lee S, Fells J, Uchiyama A, Murakami-Murofushi K, Kennel S, Wall J, Patil R, Gupte R, Balazs L, Miller DD, Tigyi GJ (2012) Controlling cancer through the autotaxin-lysophosphatidic acid receptor axis. Biochem Soc Trans 40(1):31–36
Houben AJ, Moolenaar WH (2011) Autotaxin and LPA receptor signaling in cancer. Cancer Metastasis Rev 30(3–4):557–565
Teo K, Brunton VG (2014) The role and therapeutic potential of the autotaxin-lysophosphatidate signalling axis in breast cancer. Biochem J 463(1):157–165
Barbayianni E, Kaffe E, Aidinis V, Kokotos G (2015) Autotaxin, a secreted lysophospholipase D, as a promising therapeutic target in chronic inflammation and cancer. Prog Lipid Res 58:76–96
Benesch MG, Tang X, Venkatraman G, Bekele RT, Brindley DN (2015) Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo. J Biomed Res 30. [Epub ahead of print]
Leblanc R, Peyruchaud O (2015) New insights into the autotaxin/LPA axis in cancer development and metastasis. Exp Cell Res 333(2):183–189
Tabuchi S (2015) The autotaxin-lysophosphatidic acid-lysophosphatidic acid receptor cascade: proposal of a novel potential therapeutic target for treating glioblastoma multiforme. Lipids Health Dis 14:56
Fotopoulou S, Oikonomou N, Grigorieva E, Nikitopoulou I, Paparountas T, Thanassopoulou A, Zhao Z, Xu Y, Kontoyiannis DL, Remboutsika E, Aidinis V (2010) ATX expression and LPA signalling are vital for the development of the nervous system. Dev Biol 339(2):451–464
Offermanns S, Mancino V, Revel JP, Simon MI (1997) Vascular system defects and impaired cell chemokinesis as a result of Galpha13 deficiency. Science 275(5299):533–536
Ferry G, Giganti A, Coge F, Bertaux F, Thiam K, Boutin JA (2007) Functional invalidation of the autotaxin gene by a single amino acid mutation in mouse is lethal. FEBS Lett 581(18):3572–3578
Yukiura H, Hama K, Nakanaga K, Tanaka M, Asaoka Y, Okudaira S, Arima N, Inoue A, Hashimoto T, Arai H, Kawahara A, Nishina H, Aoki J (2011) Autotaxin regulates vascular development via multiple lysophosphatidic acid (LPA) receptors in zebrafish. J Biol Chem 286(51):43972–43983
Nam SW, Clair T, Kim YS, McMarlin A, Schiffmann E, Liotta LA, Stracke ML (2001) Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor. Cancer Res 61(18):6938–6944
Xu X, Prestwich GD (2010) Inhibition of tumor growth and angiogenesis by a lysophosphatidic acid antagonist in an engineered three-dimensional lung cancer xenograft model. Cancer 116(7):1739–1750
Okudaira S, Yukiura H, Aoki J (2010) Biological roles of lysophosphatidic acid signaling through its production by autotaxin. Biochimie 92(6):698–706
Moolenaar WH, Houben AJ, Lee SJ, van Meeteren LA (2013) Autotaxin in embryonic development. Biochim Biophys Acta 1831(1):13–19
Yuelling LM, Fuss B (2008) Autotaxin (ATX): a multi-functional and multi-modular protein possessing enzymatic lysoPLD activity and matricellular properties. Biochim Biophys Acta 1781(9):525–530
Nakanaga K, Hama K, Aoki J (2010) Autotaxin--an LPA producing enzyme with diverse functions. J Biochem 148(1):13–24
Perrakis A, Moolenaar WH (2014) Autotaxin: structure-function and signaling. J Lipid Res 55(6):1010–1018
Nishimasu H, Okudaira S, Hama K, Mihara E, Dohmae N, Inoue A, Ishitani R, Takagi J, Aoki J, Nureki O (2011) Crystal structure of autotaxin and insight into GPCR activation by lipid mediators. Nat Struct Mol Biol 18(2):205–212
Hausmann J, Kamtekar S, Christodoulou E, Day JE, Wu T, Fulkerson Z, Albers HM, van Meeteren LA, Houben AJ, van Zeijl L, Jansen S, Andries M, Hall T, Pegg LE, Benson TE, Kasiem M, Harlos K, Kooi CW, Smyth SS, Ovaa H, Bollen M, Morris AJ, Moolenaar WH, Perrakis A (2011) Structural basis of substrate discrimination and integrin binding by autotaxin. Nat Struct Mol Biol 18(2):198–204
Koh E, Clair T, Woodhouse EC, Schiffmann E, Liotta L, Stracke M (2003) Site-directed mutations in the tumor-associated cytokine, autotaxin, eliminate nucleotide phosphodiesterase, lysophospholipase D, and motogenic activities. Cancer Res 63(9):2042–2045
Tabchy A, Tigyi G, Mills GB (2011) Location, location, location: a crystal-clear view of autotaxin saturating LPA receptors. Nat Struct Mol Biol 18(2):117–118
Nishimasu H, Ishitani R, Aoki J, Nureki O (2012) A 3D view of autotaxin. Trends Pharmacol Sci 33(3):138–145
Hausmann J, Perrakis A, Moolenaar WH (2013) Structure-function relationships of autotaxin, a secreted lysophospholipase D. Adv Biol Regul 53(1):112–117
Jansen S, Callewaert N, Dewerte I, Andries M, Ceulemans H, Bollen M (2007) An essential oligomannosidic glycan chain in the catalytic domain of autotaxin, a secreted lysophospholipase-D. J Biol Chem 282(15):11084–11091
Jansen S, Andries M, Derua R, Waelkens E, Bollen M (2009) Domain interplay mediated by an essential disulfide linkage is critical for the activity and secretion of the metastasis-promoting enzyme autotaxin. J Biol Chem 284(21):14296–14302
Koyama M, Nishimasu H, Ishitani R, Nureki O (2012) Molecular dynamics simulation of autotaxin: roles of the nuclease-like domain and the glycan modification. J Phys Chem B 116(39):11798–11808
Cimpean A, Stefan C, Gijsbers R, Stalmans W, Bollen M (2004) Substrate-specifying determinants of the nucleotide pyrophosphatases/phosphodiesterases NPP1 and NPP2. Biochem J 381(Pt 1):71–77
Albers HM, Hendrickx LJ, van Tol RJ, Hausmann J, Perrakis A, Ovaa H (2011) Structure-based design of novel boronic acid-based inhibitors of autotaxin. J Med Chem 54(13):4619–4626
Mize CD, Abbott AM, Gacasan SB, Parrill AL, Baker DL (2011) Ligand-based autotaxin pharmacophore models reflect structure-based docking results. J Mol Graph Model 31:76–86
Kawaguchi M, Okabe T, Okudaira S, Nishimasu H, Ishitani R, Kojima H, Nureki O, Aoki J, Nagano T (2013) Screening and X-ray crystal structure-based optimization of autotaxin (ENPP2) inhibitors, using a newly developed fluorescence probe. ASC Chem Biol 8(8):1713–1721
Norman DD, Ibezim A, Scott WE, White S, Parrill AL, Baker DL (2013) Autotaxin inhibition: development and application of computational tools to identify site-selective lead compounds. Bioorg Med Chem 21(17):5548–5560
Fells JI, Lee SC, Fujiwara Y, Norman DD, Lim KG, Tsukahara R, Liu J, Patil R, Miller DD, Kirby RJ, Nelson S, Seibel W, Papoian R, Parrill AL, Baker DL, Bittman R, Tigyi G (2013) Hits of a high-throughput screen identify the hydrophobic pocket of autotaxin/lysophospholipase D as an inhibitory surface. Mol Pharmacol 84(3):415–424
Fells JI, Lee SC, Norman DD, Tsukahara R, Kirby JR, Nelson S, Seibel W, Papoian R, Patil R, Miller DD, Parrill AL, Pham TC, Baker DL, Bittman R, Tigyi G (2014) Targeting the hydrophobic pocket of autotaxin with virtual screening of inhibitors identifies a common aromatic sulfonamide structural motif. FEBS J 281(4):1017–1028
Stein AJ, Bain G, Prodanovich P, Santini AM, Darlington J, Stelzer NM, Sidhu RS, Schaub J, Goulet L, Lonergan D, Calderon I, Evans JF, Hutchinson JH (2015) Structural basis for inhibition of human autotaxin by four potent compounds with distinct modes of binding. Mol Pharmacol 88(6):982–992
Kato K, Ikeda H, Miyakawa S, Futakawa S, Nonaka Y, Fujiwara M, Okudaira S, Kano K, Aoki J, Morita J, Ishitani R, Nishimasu H, Nakamura Y, Nureki O (2016) Structural basis for specific inhibition of Autotaxin by a DNA aptamer. Nat Struct Mol Biol 23(5):395–401
Kanda H, Newton R, Klein R, Morita Y, Gunn MD, Rosen SD (2008) Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs. Nat Immunol 9(4):415–423
Pamuklar Z, Federico L, Liu S, Umezu-Goto M, Dong A, Panchatcharam M, Fulkerson Z, Berdyshev E, Natarajan V, Fang X, van Meeteren LA, Moolenaar WH, Mills GB, Morris AJ, Smyth SS (2009) Autotaxin/lysopholipase D and lysophosphatidic acid regulate murine hemostasis and thrombosis. J Biol Chem 284(11):7385–7394
Zhao J, He D, Berdyshev E, Zhong M, Salgia R, Morris AJ, Smyth SS, Natarajan V, Zhao Y (2011) Autotaxin induces lung epithelial cell migration through lysoPLD activity-dependent and -independent pathways. Biochem J 439(1):45–55
Fulkerson Z, Wu T, Sunkara M, Kooi CV, Morris AJ, Smyth SS (2011) Binding of autotaxin to integrins localizes lysophosphatidic acid production to platelets and mammalian cells. J Biol Chem 286(40):34654–34663
Wu T, Kooi CV, Shah P, Charnigo R, Huang C, Smyth SS, Morris AJ (2014) Integrin-mediated cell surface recruitment of autotaxin promotes persistent directional cell migration. FASEB J 28(2):861–870
Jansen S, Stefan C, Creemers JW, Waelkens E, Van Eynde A, Stalmans W, Bollen M (2005) Proteolytic maturation and activation of autotaxin (NPP2), a secreted metastasis-enhancing lysophospholipase D. J Cell Sci 118(Pt 14):3081–3089
Koike S, Keino-Masu K, Ohto T, Masu M (2006) The N-terminal hydrophobic sequence of autotaxin (ENPP2) functions as a signal peptide. Genes Cells 11(2):133–142
Pradere JP, Tarnus E, Gres S, Valet P, Saulnier-Blache JS (2007) Secretion and lysophospholipase D activity of autotaxin by adipocytes are controlled by N-glycosylation and signal peptidase. Biochim Biophys Acta 1771(1):93–102
Santos AN, Riemann D, Santos AN, Kehlen A, Thiele K, Langner J (1996) Treatment of fibroblast-like synoviocytes with IFN-gamma results in the down-regulation of autotaxin mRNA. Biochem Biophys Res Commun 229(2):419–424
Kawagoe H, Stracke ML, Nakamura H, Sano K (1997) Expression and transcriptional regulation of the PD-Ialpha/autotaxin gene in neuroblastoma. Cancer Res 57(12):2516–2521
Kehlen A, Lauterbach R, Santos AN, Thiele K, Kabisch U, Weber E, Riemann D, Langner J (2001) IL-1 beta- and IL-4-induced down-regulation of autotaxin mRNA and PC-1 in fibroblast-like synoviocytes of patients with rheumatoid arthritis (RA). Clin Exp Immunol 123(1):147–154
Chen M, O’Connor KL (2005) Integrin alpha6beta4 promotes expression of autotaxin/ENPP2 autocrine motility factor in breast carcinoma cells. Oncogene 24(32):5125–5130
Farina AR, Cappabianca L, Ruggeri P, Di Ianni N, Ragone M, Merolle S, Sano K, Stracke ML, Horowitz JM, Gulino A, Mackay AR (2012) Constitutive autotaxin transcription by Nmyc-amplified and non-amplified neuroblastoma cells is regulated by a novel AP-1 and SP-mediated mechanism and abrogated by curcumin. FEBS Lett 586(20):3681–3691
Sioletic S, Czaplinski J, Hu L, Fletcher JA, Fletcher CD, Wagner AJ, Loda M, Demetri GD, Sicinska ET, Snyder EL (2014) c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas. J Pathol 234(2):190–202
Benesch MG, Zhao YY, Curtis JM, McMullen TP, Brindley DN (2015) Regulation of autotaxin expression and secretion by lysophosphatidate and sphingosine 1-phosphate. J Lipid Res 56(6):1134–1144
Song J, Guan M, Zhao Z, Zhang J (2015) Type I Interferons Function as Autocrine and Paracrine Factors to Induce Autotaxin in Response to TLR Activation. PLoS One 10(8):e0136629
Greenman R, Gorelik A, Sapir T, Baumgart J, Zamor V, Segal-Salto M, Levin-Zaidman S, Aidinis V, Aoki J, Nitsch R, Vogt J, Reiner O (2015) Non-cell autonomous and non-catalytic activities of ATX in the develo** brain. Front Neurosci 9:53
Fox MA, Colello RJ, Macklin WB, Fuss B (2003) Phosphodiesterase-Ialpha/autotaxin: a counteradhesive protein expressed by oligodendrocytes during onset of myelination. Mol Cell Neurosci 23(3):507–519
Fox MA, Alexander JK, Afshari FS, Colello RJ, Fuss B (2004) Phosphodiesterase-I alpha/autotaxin controls cytoskeletal organization and FAK phosphorylation during myelination. Mol Cell Neurosci 27(2):140–150
Dennis J, White MA, Forrest AD, Yuelling LM, Nogaroli L, Afshari FS, Fox MA, Fuss B (2008) Phosphodiesterase-Ialpha/autotaxin’s MORFO domain regulates oligodendroglial process network formation and focal adhesion organization. Mol Cell Neurosci 37(2):412–424
Dennis J, Morgan MK, Graf MR, Fuss B (2012) P2Y(12) receptor expression is a critical determinant of functional responsiveness to ATX’s MORFO domain. Purinergic Signal 8:181–190
Morrison SJ, Kimble J (2006) Asymmetric and symmetric stem-cell divisions in development and cancer. Nature 441(7097):1068–1074
Knoblich JA (2008) Mechanisms of asymmetric stem cell division. Cell 132(4):583–597
Januschke J, Nathke I (2014) Stem cell decisions: a twist of fate or a niche market? Semin Cell Dev Biol 34:116–123
Watt FM, Hogan BL (2000) Out of Eden: stem cells and their niches. Science 287(5457):1427–1430
Pebay A, Bonder CS, Pitson SM (2007) Stem cell regulation by lysophospholipids. Prostaglandins Other Lipid Mediat 84(3–4):83–97
Pitson SM, Pebay A (2009) Regulation of stem cell pluripotency and neural differentiation by lysophospholipids. Neurosignals 17(4):242–254
Bradley A, Evans M, Kaufman MH, Robertson E (1984) Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature 309(5965):255–256
Nagy A, Gocza E, Diaz EM, Prideaux VR, Ivanyi E, Markkula M, Rossant J (1990) Embryonic stem cells alone are able to support fetal development in the mouse. Development 110(3):815–821
Ilic D, Ogilvie C (2016) Human embryonic stem cells-what have we done? What are we doing? Where are we going? Stem Cells. [Epub ahead of print]
Avior Y, Sagi I, Benvenisty N (2016) Pluripotent stem cells in disease modelling and drug discovery. Nat Rev Mol Cell Biol 17(3):170–182
Verfaillie CM, Pera MF, Lansdorp PM (2002) Stem cells: hype and reality. Hematol Am Soc Hematol Educ Program 2002:369–391
Cauffman G, De Rycke M, Sermon K, Liebaers I, Van de Velde H (2009) Markers that define stemness in ESC are unable to identify the totipotent cells in human preimplantation embryos. Hum Reprod 24(1):63–70
Galan A, Diaz-Gimeno P, Poo ME, Valbuena D, Sanchez E, Ruiz V, Dopazo J, Montaner D, Conesa A, Simon C (2013) Defining the genomic signature of totipotency and pluripotency during early human development. PLoS One 8(4):e62135
Condic ML (2014) Totipotency: what it is and what it is not. Stem Cells Dev 23(8):796–812
Pebay A, Wong RC, Pitson SM, Wolvetang EJ, Peh GS, Filipczyk A, Koh KL, Tellis I, Nguyen LT, Pera MF (2005) Essential roles of sphingosine-1-phosphate and platelet-derived growth factor in the maintenance of human embryonic stem cells. Stem Cells 23(10):1541–1548
Dottori M, Leung J, Turnley AM, Pebay A (2008) Lysophosphatidic acid inhibits neuronal differentiation of neural stem/progenitor cells derived from human embryonic stem cells. Stem Cells 26(5):1146–1154
Todorova MG, Fuentes E, Soria B, Nadal A, Quesada I (2009) Lysophosphatidic acid induces Ca2+ mobilization and c-Myc expression in mouse embryonic stem cells via the phospholipase C pathway. Cell Signal 21(4):523–528
Schuck S, Soloaga A, Schratt G, Arthur JS, Nordheim A (2003) The kinase MSK1 is required for induction of c-fos by lysophosphatidic acid in mouse embryonic stem cells. BMC Mol Biol 4:6
Apati A, Paszty K, Hegedus L, Kolacsek O, Orban TI, Erdei Z, Szebenyi K, Pentek A, Enyedi A, Sarkadi B (2013) Characterization of calcium signals in human embryonic stem cells and in their differentiated offspring by a stably integrated calcium indicator protein. Cell Signal 25(4):752–759
Kobayashi T, Yamano S, Murayama S, Ishikawa H, Tokumura A, Aono T (1994) Effect of lysophosphatidic acid on the preimplantation development of mouse embryos. FEBS Lett 351(1):38–40
Ahn JI, Lee KH, Shin DM, Shim JW, Kim CM, Kim H, Lee SH, Lee YS (2004) Temporal expression changes during differentiation of neural stem cells derived from mouse embryonic stem cell. J Cell Biochem 93(3):563–578
Liszewska E, Reinaud P, Billon-Denis E, Dubois O, Robin P, Charpigny G (2009) Lysophosphatidic acid signaling during embryo development in sheep: involvement in prostaglandin synthesis. Endocrinology 150(1):422–434
Boruszewska D, Kowalczyk-Zieba I, Piotrowska-Tomala K, Saulnier-Blache JS, Acosta T, Skarzynski DJ, Woclawek-Potocka I (2013) Which bovine endometrial cells are the source of and target for lysophosphatidic acid? Reprod Biol 13(1):100–103
Brunnert D, Sztachelska M, Bornkessel F, Treder N, Wolczynski S, Goyal P, Zygmunt M (2014) Lysophosphatidic acid and sphingosine 1-phosphate metabolic pathways and their receptors are differentially regulated during decidualization of human endometrial stromal cells. Mol Hum Reprod 20(10):1016–1025
Aoki J, Inoue A, Okudaira S (2008) Two pathways for lysophosphatidic acid production. Biochim Biophys Acta 1781(9):513–518
Schofield R (1978) The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4(1–2):7–25
Morrison SJ, Spradling AC (2008) Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 132(4):598–611
Lander AD, Kimble J, Clevers H, Fuchs E, Montarras D, Buckingham M, Calof AL, Trumpp A, Oskarsson T (2012) What does the concept of the stem cell niche really mean today? BMC Biol 10:19
Sanchez-Aguilera A, Mendez-Ferrer S (2016) The hematopoietic stem-cell niche in health and leukemia. Cell Mol Life Sci. [Epub ahead of print]
Wilson A, Laurenti E, Oser G, van der Wath RC, Blanco-Bose W, Jaworski M, Offner S, Dunant CF, Eshkind L, Bockamp E, Lio P, Macdonald HR, Trumpp A (2008) Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell 135(6):1118–1129
Brenet F, Scandura JM (2015) Cutting the brakes on hematopoietic regeneration by blocking TGFbeta to limit chemotherapy-induced myelosuppression. Mol Cell Oncol 2(3):e978703
Ortlepp C, Steudel C, Heiderich C, Koch S, Jacobi A, Ryser M, Brenner S, Bornhauser M, Brors B, Hofmann WK, Ehninger G, Thiede C (2013) Autotaxin is expressed in FLT3-ITD positive acute myeloid leukemia and hematopoietic stem cells and promotes cell migration and proliferation. Exp Hematol 41(5):444–461
Lansdorp PM, Sutherland HJ, Eaves CJ (1990) Selective expression of CD45 isoforms on functional subpopulations of CD34+ hemopoietic cells from human bone marrow. J Exp Med 172(1):363–366
Lansdorp PM, Dragowska W (1992) Long-term erythropoiesis from constant numbers of CD34+ cells in serum-free cultures initiated with highly purified progenitor cells from human bone marrow. J Exp Med 175(6):1501–1509
Mayani H, Dragowska W, Lansdorp PM (1993) Cytokine-induced selective expansion and maturation of erythroid versus myeloid progenitors from purified cord blood precursor cells. Blood 81(12):3252–3258
Sidney LE, Branch MJ, Dunphy SE, Dua HS, Hopkinson A (2014) Concise review: evidence for CD34 as a common marker for diverse progenitors. Stem Cells 32(6):1380–1389
Lindner U, Kramer J, Rohwedel J, Schlenke P (2010) Mesenchymal stem or stromal cells: toward a better understanding of their biology? Transfus Med Hemother 37(2):75–83
Mendez-Ferrer S, Scadden DT, Sanchez-Aguilera A (2015) Bone marrow stem cells: current and emerging concepts. Ann N Y Acad Sci 1335:32–44
Evseenko D, Latour B, Richardson W, Corselli M, Sahaghian A, Cardinal S, Zhu Y, Chan R, Dunn B, Crooks GM (2013) Lysophosphatidic acid mediates myeloid differentiation within the human bone marrow microenvironment. PLoS One 8(5):e63718
Ryu JM, Han HJ (2015) Autotaxin-LPA axis regulates hMSC migration by adherent junction disruption and cytoskeletal rearrangement via LPAR1/3-dependent PKC/GSK3beta/beta-catenin and PKC/Rho GTPase pathways. Stem Cells 33(3):819–832
Annabi B, Thibeault S, Lee YT, Bousquet-Gagnon N, Eliopoulos N, Barrette S, Galipeau J, Beliveau R (2003) Matrix metalloproteinase regulation of sphingosine-1-phosphate-induced angiogenic properties of bone marrow stromal cells. Exp Hematol 31(7):640–649
Jaganathan BG, Ruester B, Dressel L, Stein S, Grez M, Seifried E, Henschler R (2007) Rho inhibition induces migration of mesenchymal stromal cells. Stem Cells 25(8):1966–1974
Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105(3):369–377
Rostovskaya M, Anastassiadis K (2012) Differential expression of surface markers in mouse bone marrow mesenchymal stromal cell subpopulations with distinct lineage commitment. PLoS One 7(12):e51221
Yanai N, Matsui N, Furusawa T, Okubo T, Obinata M (2000) Sphingosine-1-phosphate and lysophosphatidic acid trigger invasion of primitive hematopoietic cells into stromal cell layers. Blood 96(1):139–144
Whetton AD, Lu Y, Pierce A, Carney L, Spooncer E (2003) Lysophospholipids synergistically promote primitive hematopoietic cell chemotaxis via a mechanism involving Vav 1. Blood 102(8):2798–2802
Fuchs E (2009) The tortoise and the hair: slow-cycling cells in the stem cell race. Cell 137(5):811–819
Hsu YC, Li L, Fuchs E (2014) Emerging interactions between skin stem cells and their niches. Nat Med 20(8):847–856
Hsu YC, Li L, Fuchs E (2014) Transit-amplifying cells orchestrate stem cell activity and tissue regeneration. Cell 157(4):935–949
Rendl M, Lewis L, Fuchs E (2005) Molecular dissection of mesenchymal-epithelial interactions in the hair follicle. PLoS Biol 3(11):e331
Grisanti L, Rezza A, Clavel C, Sennett R, Rendl M (2013) Enpp2/Autotaxin in dermal papilla precursors is dispensable for hair follicle morphogenesis. J Invest Dermatol 133(10):2332–2339
Yanagida K, Masago K, Nakanishi H, Kihara Y, Hamano F, Tajima Y, Taguchi R, Shimizu T, Ishii S (2009) Identification and characterization of a novel lysophosphatidic acid receptor, p2y5/LPA6. J Biol Chem 284(26):17731–17741
Inoue A, Arima N, Ishiguro J, Prestwich GD, Arai H, Aoki J (2011) LPA-producing enzyme PA-PLA(1)alpha regulates hair follicle development by modulating EGFR signalling. EMBO J 30(20):4248–4260
Rosen JM, Jordan CT (2009) The increasing complexity of the cancer stem cell paradigm. Science (New York, NY) 324(5935):1670–1673. doi:10.1126/science.1171837
Meacham CE, Morrison SJ (2013) Tumour heterogeneity and cancer cell plasticity. Nature 501(7467):328–337
Carnero A, Garcia-Mayea Y, Mir C, Lorente J, Rubio IT, Me LL (2016) The cancer stem-cell signaling network and resistance to therapy. Cancer Treat Rev 49:25–36
Chen W, Dong J, Haiech J, Kilhoffer MC, Zeniou M (2016) Cancer Stem Cell Quiescence and Plasticity as Major Challenges in Cancer Therapy. Stem Cells Int 2016:1740936
Woodward WA, Hill RP (2016) Cancer Stem Cells. Recent Results Cancer Res 198:25–44
Gkountela S, Aceto N (2016) Stem-like features of cancer cells on their way to metastasis. Biol Direct 11:33
Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH, Nephew KP (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68(11):4311–4320
Jazaeri AA, Awtrey CS, Chandramouli GV, Chuang YE, Khan J, Sotiriou C, Aprelikova O, Yee CJ, Zorn KK, Birrer MJ, Barrett JC, Boyd J (2005) Gene expression profiles associated with response to chemotherapy in epithelial ovarian cancers. Clin Cancer Res 11(17):6300–6310
Vidot S, Witham J, Agarwal R, Greenhough S, Bamrah HS, Tigyi GJ, Kaye SB, Richardson A (2010) Autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells. Cell Signal 22(6):926–935
Seo EJ, Kwon YW, Jang IH, Kim DK, Lee SI, Choi EJ, Kim KH, Suh DS, Lee JH, Choi KU, Lee JW, Mok HJ, Kim KP, Matsumoto H, Aoki J, Kim JH (2016) Autotaxin regulates maintenance of ovarian cancer stem cells through lysophosphatidic acid-mediated autocrine mechanism. Stem Cells 34(3):551–564
Ng W, Pebay A, Drummond K, Burgess A, Kaye AH, Morokoff A (2014) Complexities of lysophospholipid signalling in glioblastoma. J Clin Neurosci 21(6):893–898
Hoelzinger DB, Mariani L, Weis J, Woyke T, Berens TJ, McDonough WS, Sloan A, Coons SW, Berens ME (2005) Gene expression profile of glioblastoma multiforme invasive phenotype points to new therapeutic targets. Neoplasia 7(1):7–16
Bhave SR, Dadey DY, Karvas RM, Ferraro DJ, Kotipatruni RP, Jaboin JJ, Hallahan AN, Dewees TA, Linkous AG, Hallahan DE, Thotala D (2013) Autotaxin inhibition with PF-8380 enhances the radiosensitivity of human and murine glioblastoma cell lines. Front Oncol 3:236
Annabi B, Lachambre MP, Plouffe K, Sartelet H, Beliveau R (2009) Modulation of invasive properties of CD133+ glioblastoma stem cells: a role for MT1-MMP in bioactive lysophospholipid signaling. Mol Carcinog 48(10):910–919
Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CL, Rich JN (2015) Cancer stem cells in glioblastoma. Genes Dev 29(12):1203–1217
Bradshaw A, Wickremsekera A, Tan ST, Peng L, Davis PF, Itinteang T (2016) Cancer Stem Cell Hierarchy in Glioblastoma Multiforme. Front Surg 3:21
Sanes DH, Reh TA, Harris WA (2011) Development of the nervous system, 3rd edn. Academic Press, Cambridge, MA
Koike S, Yutoh Y, Keino-Masu K, Noji S, Masu M, Ohuchi H (2011) Autotaxin is required for the cranial neural tube closure and establishment of the midbrain-hindbrain boundary during mouse development. Dev Dyn 240(2):413–421
Koike S, Keino-Masu K, Masu M (2010) Deficiency of autotaxin/lysophospholipase D results in head cavity formation in mouse embryos through the LPA receptor-Rho-ROCK pathway. Biochem Biophys Res Commun 400(1):66–71
Campbell K, Gotz M (2002) Radial glia: multi-purpose cells for vertebrate brain development. Trends Neurosci 25(5):235–238
Fishell G, Kriegstein AR (2003) Neurons from radial glia: the consequences of asymmetric inheritance. Curr Opin Neurobiol 13(1):34–41
Anthony TE, Klein C, Fishell G, Heintz N (2004) Radial glia serve as neuronal progenitors in all regions of the central nervous system. Neuron 41(6):881–890
Wilsch-Brauninger M, Florio M, Huttner WB (2016) Neocortex expansion in development and evolution—from cell biology to single genes. Curr Opin Neurobiol 39:122–132
Frisca F, Crombie DE, Dottori M, Goldshmit Y, Pebay A (2013) Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid. J Lipid Res 54(5):1192–1206
Cui HL, Qiao JT (2006) Promotive action of lysophosphatidic acid on proliferation of rat embryonic neural stem cells and their differentiation to cholinergic neurons in vitro. Sheng Li Xue Bao 58(6):547–555
Fukushima N, Shano S, Moriyama R, Chun J (2007) Lysophosphatidic acid stimulates neuronal differentiation of cortical neuroblasts through the LPA1-G(i/o) pathway. Neurochem Int 50(2):302–307
Miller RH (2005) Dorsally derived oligodendrocytes come of age. Neuron 45(1):1–3
Richardson WD, Kessaris N, Pringle N (2006) Oligodendrocyte wars. Nat Rev Neurosci 7(1):11–18
Miller RH (2002) Regulation of oligodendrocyte development in the vertebrate CNS. Prog Neurobiol 67(6):451–467
Yuelling LW, Waggener CT, Afshari FS, Lister JA, Fuss B (2012) Autotaxin/ENPP2 regulates oligodendrocyte differentiation in vivo in the develo** zebrafish hindbrain. Glia 60(10):1605–1618
Wheeler NA, Lister JA, Fuss B (2015) The Autotaxin-Lysophosphatidic Acid Axis Modulates Histone Acetylation and Gene Expression during Oligodendrocyte Differentiation. J Neurosci 35(32):11399–11414
Liu J, Moyon S, Hernandez M, Casaccia P (2016) Epigenetic control of oligodendrocyte development: adding new players to old keepers. Curr Opin Neurobiol 39:133–138
Weiner JA, Hecht JH, Chun J (1998) Lysophosphatidic acid receptor gene vzg-1/lpA1/edg-2 is expressed by mature oligodendrocytes during myelination in the postnatal murine brain. J Comp Neurol 398(4):587–598
Stankoff B, Barron S, Allard J, Barbin G, Noel F, Aigrot MS, Premont J, Sokoloff P, Zalc B, Lubetzki C (2002) Oligodendroglial expression of Edg-2 receptor: developmental analysis and pharmacological responses to lysophosphatidic acid. Mol Cell Neurosci 20(3):415–428
Dawson J, Hotchin N, Lax S, Rumsby M (2003) Lysophosphatidic acid induces process retraction in CG-4 line oligodendrocytes and oligodendrocyte precursor cells but not in differentiated oligodendrocytes. J Neurochem 87(4):947–957
Nogaroli L, Yuelling LM, Dennis J, Gorse K, Payne SG, Fuss B (2009) Lysophosphatidic acid can support the formation of membranous structures and an increase in MBP mRNA levels in differentiating oligodendrocytes. Neurochem Res 34(1):182–193
Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O’Keeffe S, Phatnani HP, Guarnieri P, Caneda C, Ruderisch N, Deng S, Liddelow SA, Zhang C, Daneman R, Maniatis T, Barres BA, Wu JQ (2014) An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci 34(36):11929–11947
Pfeiffer SE, Warrington AE, Bansal R (1993) The oligodendrocyte and its many cellular processes. Trends Cell Biol 3:191–197
Dugas JC, Tai YC, Speed TP, Ngai J, Barres BA (2006) Functional genomic analysis of oligodendrocyte differentiation. J Neurosci 26(43):10967–10983
Dennis J, Nogaroli L, Fuss B (2005) Phosphodiesterase-Ialpha/autotaxin (PD-Ialpha/ATX): a multifunctional protein involved in central nervous system development and disease. J Neurosci Res 82(6):737–742
Murphy-Ullrich JE (2001) The de-adhesive activity of matricellular proteins: is intermediate cell adhesion an adaptive state? J Clin Invest 107(7):785–790
Nagai J, Uchida H, Matsushita Y, Yano R, Ueda M, Niwa M, Aoki J, Chun J, Ueda H (2010) Autotaxin and lysophosphatidic acid1 receptor-mediated demyelination of dorsal root fibers by sciatic nerve injury and intrathecal lysophosphatidylcholine. Mol Pain 6:78
Inoue M, **e W, Matsushita Y, Chun J, Aoki J, Ueda H (2008) Lysophosphatidylcholine induces neuropathic pain through an action of autotaxin to generate lysophosphatidic acid. Neuroscience 152(2):296–298
Ma L, Uchida H, Nagai J, Inoue M, Aoki J, Ueda H (2010) Evidence for de novo synthesis of lysophosphatidic acid in the spinal cord through phospholipase A2 and autotaxin in nerve injury-induced neuropathic pain. J Pharmacol Exp Ther 333(2):540–546
Katsifa A, Kaffe E, Nikolaidou-Katsaridou N, Economides AN, Newbigging S, McKerlie C, Aidinis V (2015) The Bulk of Autotaxin Activity Is Dispensable for Adult Mouse Life. PLoS One 10(11):e0143083
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This work was supported by grants from the National Institute of Health (B.F) and the National Multiple Sclerosis Society (B.F.).
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Fuss, B. (2017). Autotaxin in Stem Cell Biology and Neurodevelopment. In: Pébay, A., Wong, R. (eds) Lipidomics of Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-49343-5_3
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