Stemness of Cancer Stem Cells (CSCs) May Drive Tumor Growth

Stemness is defined by the ability to self-renew and differentiate.1 Unlike normal stem cells, which differentiate into healthy, mature cell types, CSCs differentiate into cancer cells.1 The stemness of CSCs is maintained by various signaling pathways that are overactivated, including JAK/STAT, Wnt/β-catenin, Nanog, and Notch, depending on the tumor type.2-6

Stemness may enable CSCs to metastasize and regrow tumors.7 This makes CSCs phenotypically different from non-stem cancer cells and may confer therapy resistance.7 Stemness can be acquired by non-stem cancer cells as they dedifferentiate in response to multiple stimuli, possibly including conventional cancer therapies.8,9

References

  1. Reya T, Morrison S, Clarke M, Weissman I. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105-111.
  2. Kim J, Jeon H, Kim H. The molecular mechanisms underlying the therapeutic resistance of cancer stem cells. Arch Pharm Res. 2015;38(3):389-401.
  3. Karamboulas C, Ailles L. Developmental signaling pathways in cancer stem cells of solid tumors. Biochim Biophys Acta. 2013;1830(2):2481-2495.
  4. Hernandez-Vargas H, Ouzounova M, Le Calvez-Kelm F, et al. Methylome analysis reveals Jak-STAT pathway deregulation in putative breast cancer stem cells. Epigenetics. 2011;6(4):428-439.
  5. Watabe T, Miyazono K. Roles of TGF-beta family signaling in stem cell renewal and differentiation. Cell Res. 2009;19(1):103-115.
  6. Mo J, Park H, Guan K. The Hippo signaling pathway in stem cell biology and cancer. EMBO Rep. 2014;15(6):642-656.
  7. Botchkina G, Ojima I. Prostate and colon cancer stem cells as a target for anti-cancer drug development. In: Shostak S, ed. Cancer Stem Cells: Theories and Practice. Rijeka, Croatia: InTech; 2011.
  8. Lagadec C, Vlashi E, Della Donna L, Dekmezian C, Pajonk F. Radiation-induced reprogramming of breast cancer cells. Stem Cells. 2012;30(5):833-844. 9. Fabregat I, Malfettone A, Soukupova J. New insights into the crossroads between EMT and stemness in the context of cancer. J Clin Med. 2016;5(3):E37.

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