Abstract
Cancer stem cells (CSCs) possess the ability to self-renew, give rise to differentiated progeny, slowly replicate, and demonstrate resistance to chemotherapy and radiotherapy. Studies have shown that epigenetic changes, which are reversible changes to genes which do not change the DNA sequence, play a key role in giving CSCs the before mentioned characteristics. These epigenetic changes include histone modification of the ATP-binding cassette (ABC) family of transporters, DNA methylation causing silencing of tumor suppressor genes, chromatin remodeling moving nucleosome at key sites implicated in pluripotency, and noncoding RNA deregulation of key pathways implicated in stemness which results in the propagation and pathogenicity observed in CSCs. The stemlike properties and ability to repopulate tumors make the eradication of CSCs imperative for treating cancer. Clinical trials are now targeting the epigenetic mechanisms which give CSCs the ability to persist through cancer treatment. Epigenetic targeting dugs show promising clinical trial results as they combat the resistant nature of CSCs due to their frequent epigenetic changes.
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References
Alraouji NN, Al-Mohanna FH, Ghebeh H, Arafah M, Almeer R, Al-Tweigeri T, Aboussekhra A (2020) Tocilizumab potentiates cisplatin cytotoxicity and targets cancer stem cells in triple-negative breast cancer. Mol Carcinog 59(9):1041–1051. https://doi.org/10.1002/mc.23234. Epub 2020 Jun 14.
Asadzadeh Z, Mansoori B, Mohammadi A, Aghajani M, Haji-Asgarzadeh K, Safarzadeh E et al (2019) microRNAs in cancer stem cells: biology, pathways, and therapeutic opportunities. J Cell Physiol 234:10002–10017. https://doi.org/10.1002/jcp.27885
Cardenas H, Vieth E, Lee J, Segar M, Liu Y, Nephew KP, Matei D (2014) TGF-β induces global changes in DNA methylation during the epithelial-to-mesenchymal transition in ovarian cancer cells. Epigenetics 9(11):1461–1472. https://doi.org/10.4161/15592294.2014.971608
Casanova J (2012) Stemness as a cell default state. EMBO Rep 13(5):396–397
D’Anello L, Sansone P, Storci G et al (2010) Epigenetic control of the basal-like gene expression profile via Interleukin-6 in breast cancer cells. Mol Cancer 9:300. https://doi.org/10.1186/1476-4598-9-300
Deaton AM, Bird A (2011) CpG islands and the regulation of transcription. Genes Dev 25(10):1010–1022. https://doi.org/10.1101/gad.2037511
Drost J, Agami R (2009) Transformation locked in a loop. Cell 139(4):654–656. https://doi.org/10.1016/j.cell.2009.10.035
Dzobo K, Vogelsang M, Thomford NE, Dandara C, Kallmeyer K, Pepper MS, Parker MI (2016, Article ID 4842134, 17 pages, 2016) Wharton’s Jelly-derived mesenchymal stromal cells and fibroblast-derived extracellular matrix synergistically activate apoptosis in a p21-dependent mechanism in WHCO1 and MDA MB 231 cancer cells in vitro. Stem Cells Int. https://doi.org/10.1155/2016/4842134
Eppert K, Takenaka K, Lechman ER, Waldron L, Nilsson B, van Galen P, Metzeler KH, Poeppl A, Ling V, Beyene J, Canty AJ, Danska JS, Bohlander SK, Buske C, Minden MD, Golub TR, Jurisica I, Ebert BL, Dick JE (2011) Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med 17(9):1086–1093. https://doi.org/10.1038/nm.2415. PMID: 21873988
French R, Pauklin S (2021) Epigenetic regulation of cancer stem cell formation and maintenance. Int J Cancer 148:2884–2897. https://doi.org/10.1002/ijc.33398
Friedmann-Morvinski D, Verma IM (2014) Dedifferentiation and reprogramming: origins of cancer stem cells. EMBO Rep 15(3):244–253. https://doi.org/10.1002/embr.201338254
Gasparini P, Bertolini G, Binda M, Magnifico A, Albano L, Tortoreto M, Pratesi G, Facchinetti F, Abolafio G, Roz L et al (2010) Molecular cytogenetic characterization of stem-like cancer cells isolated from established cell lines. Cancer Lett 296:206–215. https://doi.org/10.1016/j.canlet.2010.04.009
Ghoshal K, Datta J, Majumder S, Bai S, Kutay H, Motiwala T, Jacob ST (2005) 5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal. Mol Cell Biol 25(11):4727–4741. https://doi.org/10.1128/MCB.25.11.4727-4741.2005. Erratum in: Mol Cell Biol. 2018 Apr 30;38(10)
Gupta PB, Fillmore CM, Jiang G, Shapira SD, Tao K, Kuperwasser C, Lander ES (2011) Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell 146:633–644. https://doi.org/10.1016/j.cell.2011.07.026
Hu Y, Yan F, Ying L, Xu D (2017) Emerging roles for epigenetic programming in the control of inflammatory signaling integration in heath and disease. Adv Exp Med Biol 1024:63–90. https://doi.org/10.1007/978-981-10-5987-2_3
Huang F-Y et al (2016) Interleukin-1β increases the risk of gastric cancer through induction of aberrant DNA methylation in a mouse model. Oncol Lett 11(4):2919–2924. https://doi.org/10.3892/ol.2016.4296
Juttermann R, Li E, Jaenisch R (1994) Toxicity of 5-aza-2′-deoxycytidine to mammalian cells is mediated primarily by covalent trap** of DNA methyltransferase rather than DNA demethylation. Proc Natl Acad Sci U S A 91:11797–11801
Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367(6464):645–648. https://doi.org/10.1038/367645a0. PMID: 7509044
Liu CC, Lin JH, Hsu TW, Su K, Li AF, Hsu HS, Hung SC (2015) IL-6 enriched lung cancer stem-like cell population by inhibition of cell cycle regulators via DNMT1 upregulation. Int J Cancer 136:547–559
Liu Z et al (2021) Epigenetic signaling of cancer stem cells during inflammation. Front Cell Dev Biol 9:772211. https://doi.org/10.3389/fcell.2021.772211
Mazzoldi EL, Pastò A, Pilotto G et al (2020) Comparison of the genomic profile of cancer stem cells and their non-stem counterpart: the case of ovarian cancer. J Clin Med 9(2):368. Published 2020 Jan 29. https://doi.org/10.3390/jcm9020368
Olsen EA, Kim YH, Kuzel TM, Pacheco TR, Foss FM, Parker S, Frankel SR, Chen C, Ricker JL, Arduino JM, Duvic M (2007) Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 25:3109–3115. https://doi.org/10.1200/JCO.2006.10.2434
Pagotto A, Pilotto G, Mazzoldi EL, Nicoletto MO, Frezzini S, Pasto A, Amadori A (2017) Autophagy inhibition reduces chemoresistance and tumorigenic potential of human ovarian cancer stem cells. Cell Death Dis 8:e2943. https://doi.org/10.1038/cddis.2017.327
Pan Y, Ma S, Cao K, Zhou S, Zhao A, Li M et al (2018) Therapeutic approaches targeting cancer stem cells. J Cancer Res Ther 14:1469–1475. https://doi.org/10.4103/jcrt.JCRT_976_17
Piekarz RL, Frye R, Turner M, Wright JJ, Allen SL, Kirschbaum MH, Zain J, Prince HM, Leonard JP, Geskin LJ et al (2009) Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27:5410–5417. https://doi.org/10.1200/JCO.2008.21.6150
Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414(6859):105–111. https://doi.org/10.1038/35102167. PMID: 11689955
Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F et al (2012) EMT and dissemination precede pancreatic tumor formation. Cell 148:349–361. https://doi.org/10.1016/j.cell.2011.11.025
Scheel C, Weinberg RA (2012) Cancer stem cells and epithelial-mesenchymal transition: concepts and molecular links. Semin Cancer Biol 22(5–6):396–403. https://doi.org/10.1016/j.semcancer.2012.04.001. Epub 2012 Apr 23.
Sun L, Mathews LA, Cabarcas SM, Zhang X, Yang A, Zhang Y, Young MR, Klarmann KD, Keller JR, Farrar WL (2013) Epigenetic regulation of SOX9 by the NF-κB signaling pathway in pancreatic cancer stem cells. Stem Cells 31(8):1454–1466. https://doi.org/10.1002/stem.1394
To KK, Polgar O, Huff LM, Morisaki K, Bates SE (2008) Histone modifications at the ABCG2 promoter following treatment with histone deacetylase inhibitor mirror those in multidrug-resistant cells. Mol Cancer Res 6(1):151–164. https://doi.org/10.1158/1541-7786.MCR-07-0175
Toh TB et al (2017) Epigenetics in cancer stem cells. Mol Cancer 16(1):29. https://doi.org/10.1186/s12943-017-0596-9
Travaglini L, Vian L, Billi M, Grignani F, Nervi C (2009) Epigenetic reprogramming of breast cancer cells by valproic acid occurs regardless of estrogen receptor status. Int J Biochem Cell Biol 41:225–234. https://doi.org/10.1016/j.biocel.2008.08.019
Yu Z, Pestell TG, Lisanti MP, Pestell RG (2012) Cancer stem cells. Int J Biochem Cell Biol 44(12):2144–2151
Wainwright EN, Scaffidi P (2017) Epigenetics and cancer stem cells: unleashing, hijacking, and restricting cellular plasticity. Trends Cancer 3(5):372–386. https://doi.org/10.1016/j.trecan.2017.04.004
Zipori D (2006) The stem state: mesenchymal plasticity as a paradigm. Curr Stem Cell Res Ther 1:95–102. https://doi.org/10.2174/157488806775269133
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Masoudi, M. (2023). The Genetic and Epigenetic Landscape of Cancer Stem Cells. In: Islam, F., Lam, A.K. (eds) Cancer Stem Cells: Basic Concept and Therapeutic Implications. Springer, Singapore. https://doi.org/10.1007/978-981-99-3185-9_4
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