Skip to main content

Advertisement

SpringerLink
Log in

Therapeutic potential of cancer stem cells

  • Review Article
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Cancer stem cells (CSCs) play an important role in cancer growth, self-renewal, metastasis, recurrence and radio/chemotherapy. However, the underlying mechanisms remain elusive. In this review, we explore the roles of CSCs in cancer’s relapse and progression and discuss the biomarkers of CSCs to predict clinical outcome and their diagnostic potential. The different approaches of CSC therapies are also reviewed, including cytotoxic, radiation, differentiation and targeting signaling pathways. We also discuss the challenge of targeting CSCs in cancer therapy. In addition, non-coding RNAs in CSC therapies are also discussed.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, et al. Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res. 2009;69(8):3382–9. doi:10.1158/0008-5472.CAN-08-4418.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3(7):730–7.

    Article  CAS  PubMed  Google Scholar 

  3. Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, et al. Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res. 2008;68(11):4311–20. doi:10.1158/0008-5472.CAN-08-0364.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432(7015):396–401. doi:10.1038/nature03128.

    Article  CAS  PubMed  Google Scholar 

  5. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67(3):1030–7. doi:10.1158/0008-5472.CAN-06-2030.

    Article  CAS  PubMed  Google Scholar 

  6. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1(5):555–67. doi:10.1016/j.stem.2007.08.014.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Qin J, Liu X, Laffin B, Chen X, Choy G, Jeter CR, et al. The PSA(-/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration. Cell Stem Cell. 2012;10(5):556–69. doi:10.1016/j.stem.2012.03.009.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Yang ZF, Ngai P, Ho DW, Yu WC, Ng MN, Lau CK, et al. Identification of local and circulating cancer stem cells in human liver cancer. Hepatology. 2008;47(3):919–28. doi:10.1002/hep.22082.

    Article  CAS  PubMed  Google Scholar 

  9. Oonishi K, Cui X, Hirakawa H, Fujimori A, Kamijo T, Yamada S, et al. Different effects of carbon ion beams and X-rays on clonogenic survival and DNA repair in human pancreatic cancer stem-like cells. Radiother Oncol. 2012;105(2):258–65. doi:10.1016/j.radonc.2012.08.009.

    Article  CAS  PubMed  Google Scholar 

  10. Xue Z, Yan H, Li J, Liang S, Cai X, Chen X, et al. Identification of cancer stem cells in vincristine preconditioned SGC7901 gastric cancer cell line. J Cell Biochem. 2012;113(1):302–12. doi:10.1002/jcb.23356.

    Article  CAS  PubMed  Google Scholar 

  11. Adikrisna R, Tanaka S, Muramatsu S, Aihara A, Ban D, Ochiai T, et al. Identification of pancreatic cancer stem cells and selective toxicity of chemotherapeutic agents. Gastroenterology. 2012;143(1):234–45. doi:10.1053/j.gastro.2012.03.054.

    Article  CAS  PubMed  Google Scholar 

  12. Fan X, Khaki L, Zhu TS, Soules ME, Talsma CE, Gul N, et al. NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells (Dayton, Ohio). 2010;28(1):5–16. doi:10.1002/stem.254.

    CAS  Google Scholar 

  13. Chang WW, Lin RJ, Yu J, Chang WY, Fu CH, Lai AC, et al. The expression and significance of insulin-like growth factor-1 receptor and its pathway on breast cancer stemprogenitors. Breast Cancer Res BCR. 2013;15(3):R39. doi:10.1186/bcr3423.

    Article  CAS  Google Scholar 

  14. Suva ML, Rheinbay E, Gillespie SM, Patel AP, Wakimoto H, Rabkin SD, et al. Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell. 2014;157(3):580–94. doi:10.1016/j.cell.2014.02.030.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Chan CH, Morrow JK, Li CF, Gao Y, Jin G, Moten A, et al. Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression. Cell. 2013;154(3):556–68. doi:10.1016/j.cell.2013.06.048.

    Article  CAS  PubMed  Google Scholar 

  16. Metellus P, Nanni-Metellus I, Delfino C, Colin C, Tchogandjian A, Coulibaly B, et al. Prognostic impact of CD133 mRNA expression in 48 glioblastoma patients treated with concomitant radiochemotherapy: a prospective patient cohort at a single institution. Ann Surg Oncol. 2011;18(10):2937–45. doi:10.1245/s10434-011-1703-6.

    Article  PubMed  Google Scholar 

  17. Giampieri R, Scartozzi M, Loretelli C, Piva F, Mandolesi A, Lezoche G, et al. Cancer stem cell gene profile as predictor of relapse in high risk stage II and stage III, radically resected colon cancer patients. PLoS One. 2013;8(9):e72843. doi:10.1371/journal.pone.0072843.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Artells R, Moreno I, Diaz T, Martinez F, Gel B, Navarro A, et al. Tumour CD133 mRNA expression and clinical outcome in surgically resected colorectal cancer patients. Eur J Cancer. 2010;46(3):642–9. doi:10.1016/j.ejca.2009.11.003.

    Article  CAS  PubMed  Google Scholar 

  19. Gottschling S, Jensen K, Warth A, Herth FJ, Thomas M, Schnabel PA, et al. Stage-specific embryonic antigen-4 is expressed in basaloid lung cancer and associated with poor prognosis. Eur Respir J. 2013;41(3):656–63. doi:10.1183/09031936.00225711.

    Article  CAS  PubMed  Google Scholar 

  20. Liu Z, Li Q, Li K, Chen L, Li W, Hou M, et al. Telomerase reverse transcriptase promotes epithelial-mesenchymal transition and stem cell-like traits in cancer cells. Oncogene. 2013;32(36):4203–13. doi:10.1038/onc.2012.441.

    Article  CAS  PubMed  Google Scholar 

  21. Mustjoki S, Richter J, Barbany G, Ehrencrona H, Fioretos T, Gedde-Dahl T, et al. Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients. Leukemia. 2013;27(7):1520–6. doi:10.1038/leu.2013.19.

    Article  CAS  PubMed  Google Scholar 

  22. Pollard SM, Yoshikawa K, Clarke ID, Danovi D, Stricker S, Russell R, et al. Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell. 2009;4(6):568–80. doi:10.1016/j.stem.2009.03.014.

    Article  CAS  PubMed  Google Scholar 

  23. Zhao X, Zhao YJ, Lin Q, Yu L, Liu Z, Lindsay H, et al. Cytogenetic landscape of paired neurospheres and traditional monolayer cultures in pediatric malignant brain tumors. Neuro-oncology. 2014;. doi:10.1093/neuonc/nou337.

    Google Scholar 

  24. Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, et al. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell. 2010;140(1):62–73. doi:10.1016/j.cell.2009.12.007.

    Article  CAS  PubMed  Google Scholar 

  25. Choi JW, Kim JK, Choi M, Kim YR, Yun SH. In vivo imaging of Lgr5-positive cell populations using confocal laser endomicroscopy during early colon tumorigenesis. Endoscopy. 2014;46(12):1110–6. doi:10.1055/s-0034-1377631.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Yilmaz OH, Valdez R, Theisen BK, Guo W, Ferguson DO, Wu H, et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature. 2006;441(7092):475–82. doi:10.1038/nature04703.

    Article  CAS  PubMed  Google Scholar 

  27. Sachlos E, Risueno RM, Laronde S, Shapovalova Z, Lee JH, Russell J, et al. Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells. Cell. 2012;149(6):1284–97. doi:10.1016/j.cell.2012.03.049.

    Article  CAS  PubMed  Google Scholar 

  28. Grimm M, Krimmel M, Polligkeit J, Alexander D, Munz A, Kluba S, et al. ABCB5 expression and cancer stem cell hypothesis in oral squamous cell carcinoma. Eur J Cancer. 2012;48(17):3186–97. doi:10.1016/j.ejca.2012.05.027.

    Article  CAS  PubMed  Google Scholar 

  29. Frank NY, Margaryan A, Huang Y, Schatton T, Waaga-Gasser AM, Gasser M, et al. ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res. 2005;65(10):4320–33. doi:10.1158/0008-5472.CAN-04-3327.

    Article  CAS  PubMed  Google Scholar 

  30. Wurth R, Pattarozzi A, Gatti M, Bajetto A, Corsaro A, Parodi A, et al. Metformin selectively affects human glioblastoma tumor-initiating cell viability: a role for metformin-induced inhibition of Akt. Cell Cycle (Georgetown, Tex). 2013;12(1):145–56. doi:10.4161/cc.23050.

    Article  CAS  Google Scholar 

  31. Guzman ML, Li X, Corbett CA, Rossi RM, Bushnell T, Liesveld JL, et al. Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione (TDZD-8). Blood. 2007;110(13):4436–44. doi:10.1182/blood-2007-05-088815.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444(7120):756–60. doi:10.1038/nature05236.

    Article  CAS  PubMed  Google Scholar 

  33. Xu Y, Stamenkovic I, Yu Q. CD44 attenuates activation of the hippo signaling pathway and is a prime therapeutic target for glioblastoma. Cancer Res. 2010;70(6):2455–64. doi:10.1158/0008-5472.CAN-09-2505.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Androutsellis-Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW, et al. Notch signalling regulates stem cell numbers in vitro and in vivo. Nature. 2006;442(7104):823–6. doi:10.1038/nature04940.

    Article  CAS  PubMed  Google Scholar 

  35. Kwon C, Cheng P, King IN, Andersen P, Shenje L, Nigam V, et al. Notch post-translationally regulates beta-catenin protein in stem and progenitor cells. Nat Cell Biol. 2011;13(10):1244–51. doi:10.1038/ncb2313.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Wang S, Sdrulla AD, diSibio G, Bush G, Nofziger D, Hicks C, et al. Notch receptor activation inhibits oligodendrocyte differentiation. Neuron. 1998;21(1):63–75.

    Article  PubMed  Google Scholar 

  37. Nicolas M, Wolfer A, Raj K, Kummer JA, Mill P, van Noort M, et al. Notch1 functions as a tumor suppressor in mouse skin. Nat Genet. 2003;33(3):416–21. doi:10.1038/ng1099.

    Article  CAS  PubMed  Google Scholar 

  38. Tonon G, Modi S, Wu L, Kubo A, Coxon AB, Komiya T, et al. t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway. Nat Genet. 2003;33(2):208–13. doi:10.1038/ng1083.

    Article  CAS  PubMed  Google Scholar 

  39. Pannuti A, Foreman K, Rizzo P, Osipo C, Golde T, Osborne B, et al. Targeting notch to target cancer stem cells. Clin Cancer Res. 2010;16(12):3141–52. doi:10.1158/1078-0432.CCR-09-2823.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Hovinga KE, Shimizu F, Wang R, Panagiotakos G, Van Der Heijden M, Moayedpardazi H, et al. Inhibition of notch signaling in glioblastoma targets cancer stem cells via an endothelial cell intermediate. Stem Cells (Dayton, Ohio). 2010;28(6):1019–29. doi:10.1002/stem.429.

    Article  CAS  Google Scholar 

  41. Wang J, Wakeman TP, Lathia JD, Hjelmeland AB, Wang XF, White RR, et al. Notch promotes radioresistance of glioma stem cells. Stem Cells (Dayton, Ohio). 2010;28(1):17–28. doi:10.1002/stem.261.

    CAS  Google Scholar 

  42. Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W. Beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell. 2001;105(4):533–45.

    Article  CAS  PubMed  Google Scholar 

  43. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17(1):9–26. doi:10.1016/j.devcel.2009.06.016.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature. 2003;423(6938):448–52. doi:10.1038/nature01611.

    Article  CAS  PubMed  Google Scholar 

  45. Greco V, Chen T, Rendl M, Schober M, Pasolli HA, Stokes N, et al. A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell. 2009;4(2):155–69. doi:10.1016/j.stem.2008.12.009.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Sokol SY. Maintaining embryonic stem cell pluripotency with Wnt signaling. Development. 2011;138(20):4341–50. doi:10.1242/dev.066209.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Polakis P. The many ways of Wnt in cancer. Curr Opin Genet Dev. 2007;17(1):45–51. doi:10.1016/j.gde.2006.12.007.

    Article  CAS  PubMed  Google Scholar 

  48. Fearon ER. PARsing the phrase “all in for Axin”-Wnt pathway targets in cancer. Cancer Cell. 2009;16(5):366–8. doi:10.1016/j.ccr.2009.10.007.

    Article  CAS  PubMed  Google Scholar 

  49. Barker N, Clevers H. Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov. 2006;5(12):997–1014. doi:10.1038/nrd2154.

    Article  CAS  PubMed  Google Scholar 

  50. Fodde R, Brabletz T. Wnt/beta-catenin signaling in cancer stemness and malignant behavior. Curr Opin Cell Biol. 2007;19(2):150–8. doi:10.1016/j.ceb.2007.02.007.

    Article  CAS  PubMed  Google Scholar 

  51. Arend RC, Londono-Joshi AI, Straughn JM Jr, Buchsbaum DJ. The Wnt/beta-catenin pathway in ovarian cancer: a review. Gynecol Oncol. 2013;131(3):772–9. doi:10.1016/j.ygyno.2013.09.034.

    Article  CAS  PubMed  Google Scholar 

  52. Mao J, Fan S, Ma W, Fan P, Wang B, Zhang J, et al. Roles of Wnt/beta-catenin signaling in the gastric cancer stem cells proliferation and salinomycin treatment. Cell Death Dis. 2014;5:e1039. doi:10.1038/cddis.2013.515.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Xia H, Cheung WK, Sze J, Lu G, Jiang S, Yao H, et al. miR-200a regulates epithelial-mesenchymal to stem-like transition via ZEB2 and beta-catenin signaling. J Biol Chem. 2010;285(47):36995–7004. doi:10.1074/jbc.M110.133744.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Han M, Liu M, Wang Y, Chen X, Xu J, Sun Y, et al. Antagonism of miR-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2 inactivation by targeting PTEN. PLoS One. 2012;7(6):e39520. doi:10.1371/journal.pone.0039520.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Li J, Zhou BP. Activation of beta-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters. BMC Cancer. 2011;11:49. doi:10.1186/1471-2407-11-49.

    Article  PubMed Central  PubMed  Google Scholar 

  56. Vlahos CJ, Matter WF, Hui KY, Brown RF. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem. 1994;269(7):5241–8.

    CAS  PubMed  Google Scholar 

  57. Palomero T, Sulis ML, Cortina M, Real PJ, Barnes K, Ciofani M, et al. Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med. 2007;13(10):1203–10. doi:10.1038/nm1636.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Trinh XB, Tjalma WA, Vermeulen PB, Van den Eynden G, Van der Auwera I, Van Laere SJ, et al. The VEGF pathway and the AKT/mTOR/p70S6K1 signalling pathway in human epithelial ovarian cancer. Br J Cancer. 2009;100(6):971–8. doi:10.1038/sj.bjc.6604921.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Wang J, Lu Y, Koch AE, Zhang J, Taichman RS. CXCR6 induces prostate cancer progression by the AKT mammalian target of rapamycin signaling pathway. Cancer Res. 2008;68(24):10367–76. doi:10.1158/0008-5472.can-08-2780.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Chen B, Xue Z, Yang G, Shi B, Yang B, Yan Y, et al. Akt-signal integration is involved in the differentiation of embryonal carcinoma cells. PLoS One. 2013;8(6):e64877. doi:10.1371/journal.pone.0064877.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Aldaz B, Sagardoy A, Nogueira L, Guruceaga E, Grande L, Huse JT, et al. Involvement of miRNAs in the differentiation of human glioblastoma multiforme stem-like cells. PLoS One. 2013;8(10):e77098. doi:10.1371/journal.pone.0077098.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Rampazzo E, Persano L, Pistollato F, Moro E, Frasson C, Porazzi P, et al. Wnt activation promotes neuronal differentiation of glioblastoma. Cell Death Dis. 2013;4:e500. doi:10.1038/cddis.2013.32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. He J, Liu Y, Zhu T, Zhu J, Dimeco F, Vescovi AL, et al. CD90 is identified as a marker for cancer stem cells in primary high-grade gliomas using tissue microarrays. Mol Cell Proteomics MCP. 2012;11(6):M111 010744. doi:10.1074/mcp.M111.010744.

    Article  Google Scholar 

  64. Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009;138(4):645–59. doi:10.1016/j.cell.2009.06.034.

    Article  CAS  PubMed  Google Scholar 

  65. Campos B, Wan F, Farhadi M, Ernst A, Zeppernick F, Tagscherer KE, et al. Differentiation therapy exerts antitumor effects on stem-like glioma cells. Clin Cancer Res. 2010;16(10):2715–28. doi:10.1158/1078-0432.CCR-09-1800.

    Article  CAS  PubMed  Google Scholar 

  66. Azzi S, Bruno S, Giron-Michel J, Clay D, Devocelle A, Croce M, et al. Differentiation therapy: targeting human renal cancer stem cells with interleukin 15. J Natl Cancer Inst. 2011;103(24):1884–98. doi:10.1093/jnci/djr451.

    Article  CAS  PubMed  Google Scholar 

  67. Kugel JF, Goodrich JA. Non-coding RNAs: key regulators of mammalian transcription. Trends Biochem Sci. 2012;37(4):144–51. doi:10.1016/j.tibs.2011.12.003.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Tsai MC, Spitale RC, Chang HY. Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res. 2011;71(1):3–7. doi:10.1158/0008-5472.CAN-10-2483.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007;131(6):1109–23. doi:10.1016/j.cell.2007.10.054.

    Article  CAS  PubMed  Google Scholar 

  70. Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, et al. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell. 2009;138(3):592–603. doi:10.1016/j.cell.2009.07.011.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Song SJ, Poliseno L, Song MS, Ala U, Webster K, Ng C, et al. MicroRNA-antagonism regulates breast cancer stemness and metastasis via TET-family-dependent chromatin remodeling. Cell. 2013;154(2):311–24. doi:10.1016/j.cell.2013.06.026.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Song SJ, Ito K, Ala U, Kats L, Webster K, Sun SM, et al. The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation. Cell Stem Cell. 2013;13(1):87–101. doi:10.1016/j.stem.2013.06.003.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Hwang WL, Jiang JK, Yang SH, Huang TS, Lan HY, Teng HW, et al. MicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer stem cells. Nat Cell Biol. 2014;16(3):268–80. doi:10.1038/ncb2910.

    Article  CAS  PubMed  Google Scholar 

  74. Cui TX, Kryczek I, Zhao L, Zhao E, Kuick R, Roh MH, et al. Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2. Immunity. 2013;39(3):611–21. doi:10.1016/j.immuni.2013.08.025.

    Article  CAS  PubMed  Google Scholar 

  75. Chang CJ, Chao CH, Xia W, Yang JY, Xiong Y, Li CW, et al. p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol. 2011;13(3):317–23. doi:10.1038/ncb2173.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142(3):409–19. doi:10.1016/j.cell.2010.06.040.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Loewer S, Cabili MN, Guttman M, Loh YH, Thomas K, Park IH, et al. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet. 2010;42(12):1113–7. doi:10.1038/ng.710.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6. doi:10.1038/nature08975.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Sun M, Liu XH, Wang KM, Nie FQ, Kong R, Yang JS, et al. Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transition. Molecular cancer. 2014;13:68. doi:10.1186/1476-4598-13-68.

    Article  PubMed Central  PubMed  Google Scholar 

  80. Luo M, Li Z, Wang W, Zeng Y, Liu Z, Qiu J. Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression. Cancer Lett. 2013;333(2):213–21. doi:10.1016/j.canlet.2013.01.033.

    Article  CAS  PubMed  Google Scholar 

  81. Bolton-Gillespie E, Schemionek M, Klein HU, Flis S, Hoser G, Lange T, et al. Genomic instability may originate from imatinib-refractory chronic myeloid leukemia stem cells. Blood. 2013;121(20):4175–83. doi:10.1182/blood-2012-11-466938.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  82. Nieborowska-Skorska M, Kopinski PK, Ray R, Hoser G, Ngaba D, Flis S, et al. Rac2-MRC-cIII-generated ROS cause genomic instability in chronic myeloid leukemia stem cells and primitive progenitors. Blood. 2012;119(18):4253–63. doi:10.1182/blood-2011-10-385658.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. de Sousa EMF, Colak S, Buikhuisen J, Koster J, Cameron K, de Jong JH, et al. Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients. Cell Stem Cell. 2011;9(5):476–85. doi:10.1016/j.stem.2011.10.008.

    Article  Google Scholar 

  84. Peter ME. Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle (Georgetown, Tex). 2009;8(6):843–52.

    Article  CAS  Google Scholar 

  85. Yang X, Lin X, Zhong X, Kaur S, Li N, Liang S, et al. Double-negative feedback loop between reprogramming factor LIN28 and microRNA let-7 regulates aldehyde dehydrogenase 1-positive cancer stem cells. Cancer Res. 2010;70(22):9463–72. doi:10.1158/0008-5472.CAN-10-2388.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  86. Kong D, Heath E, Chen W, Cher ML, Powell I, Heilbrun L, et al. Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM. PLoS One. 2012;7(3):e33729. doi:10.1371/journal.pone.0033729.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Dillman RO, Cornforth AN, Depriest C, McClay EF, Amatruda TT, de Leon C, et al. Tumor stem cell antigens as consolidative active specific immunotherapy: a randomized phase II trial of dendritic cells versus tumor cells in patients with metastatic melanoma. J Immunother. 2012;35(8):641–9. doi:10.1097/CJI.0b013e31826f79c8.

    Article  PubMed  Google Scholar 

  88. Kreso A, van Galen P, Pedley NM, Lima-Fernandes E, Frelin C, Davis T, et al. Self-renewal as a therapeutic target in human colorectal cancer. Nat Med. 2014;20(1):29–36. doi:10.1038/nm.3418.

    Article  CAS  PubMed  Google Scholar 

  89. Curry JM, Tuluc M, Whitaker-Menezes D, Ames JA, Anantharaman A, Butera A, et al. Cancer metabolism, stemness and tumor recurrence: MCT1 and MCT4 are functional biomarkers of metabolic symbiosis in head and neck cancer. Cell Cycle (Georgetown, Tex). 2013;12(9):1371–84. doi:10.4161/cc.24092.

    Article  CAS  Google Scholar 

  90. Le XF, Arachchige-Don AS, Mao W, Horne MC, Bast RC Jr. Roles of human epidermal growth factor receptor 2, c-jun NH2-terminal kinase, phosphoinositide 3-kinase, and p70 S6 kinase pathways in regulation of cyclin G2 expression in human breast cancer cells. Mol Cancer Ther. 2007;6(11):2843–57. doi:10.1158/1535-7163.MCT-07-0109.

    Article  CAS  PubMed  Google Scholar 

  91. Yang C, Peng J, Jiang W, Zhang Y, Chen X, Wu X, et al. mTOR activation in immature cells of primary nasopharyngeal carcinoma and anti-tumor effect of rapamycin in vitro and in vivo. Cancer Lett. 2013;341(2):186–94. doi:10.1016/j.canlet.2013.08.004.

    Article  CAS  PubMed  Google Scholar 

  92. Kemper K, Prasetyanti PR, De Lau W, Rodermond H, Clevers H, Medema JP. Monoclonal antibodies against Lgr5 identify human colorectal cancer stem cells. Stem Cells (Dayton, Ohio). 2012;30(11):2378–86. doi:10.1002/stem.1233.

    Article  CAS  Google Scholar 

  93. Lacy MQ, Alsina M, Fonseca R, Paccagnella ML, Melvin CL, Yin D, et al. Phase I, pharmacokinetic and pharmacodynamic study of the anti-insulinlike growth factor type 1 Receptor monoclonal antibody CP-751,871 in patients with multiple myeloma. J Clin Oncol. 2008;26(19):3196–203. doi:10.1200/jco.2007.15.9319.

    Article  CAS  PubMed  Google Scholar 

  94. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. doi:10.1016/j.cell.2011.02.013.

    Article  CAS  PubMed  Google Scholar 

  95. Lonardo E, Frias-Aldeguer J, Hermann PC, Heeschen C. Pancreatic stellate cells form a niche for cancer stem cells and promote their self-renewal and invasiveness. Cell Cycle (Georgetown, Tex). 2012;11(7):1282–90. doi:10.4161/cc.19679.

    Article  CAS  Google Scholar 

  96. Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B, et al. A perivascular niche for brain tumor stem cells. Cancer Cell. 2007;11(1):69–82. doi:10.1016/j.ccr.2006.11.020.

    Article  CAS  PubMed  Google Scholar 

  97. Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T. Opinion: migrating cancer stem cells—an integrated concept of malignant tumour progression. Nat Rev Cancer. 2005;5(9):744–9. doi:10.1038/nrc1694.

    Article  CAS  PubMed  Google Scholar 

  98. Yu X, Jiang X, Li H, Guo L, Jiang W, Lu SH. miR-203 inhibits the proliferation and self-renewal of esophageal cancer stem-like cells by suppressing stem renewal factor Bmi-1. Stem Cells Dev. 2014;23(6):576–85. doi:10.1089/scd.2013.0308.

    Article  CAS  PubMed  Google Scholar 

  99. Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22(7):894–907. doi:10.1101/gad.1640608.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  100. Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, et al. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008;9(6):582–9. doi:10.1038/embor.2008.74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that there is no conflict of interests regarding the publication of this paper.

Author information

Authors and Affiliations

  1. Department of Otorhinolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Chunguang Yang

  2. Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA

    Kunlin Jin

  3. Department of Neurology, Changsha Central Hospital, Changsha, Hunan, China

    Yangping Tong

  4. Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong

    William Chi Cho

Authors
  1. Chunguang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kunlin Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yangping Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William Chi Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William Chi Cho.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, C., Jin, K., Tong, Y. et al. Therapeutic potential of cancer stem cells. Med Oncol 32, 170 (2015). https://doi.org/10.1007/s12032-015-0619-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-015-0619-6

Keywords

Search

Navigation