Cancer stem cells in head and neck cancer

Cancers

Volumn 3, Issue 1, 2011, Pages 415-427

  Mitra, Doyel ^a   Malkoski, Stephen P ^a   Wang, Xiao Jing ^a  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

Author keywords

Chemoresistance; Radioresistance; Transplantation; Tumorigenicity

Indexed keywords

CYTOTOXIC AGENT; HERMES ANTIGEN;

ACUTE GRANULOCYTIC LEUKEMIA; ANTIGEN EXPRESSION; CANCER CLASSIFICATION; CANCER MORTALITY; CANCER RADIOTHERAPY; CANCER RESISTANCE; CANCER STEM CELL; CANCER SURVIVAL; CARCINOGENESIS; CELL HETEROGENEITY; EPITHELIAL MESENCHYMAL TRANSITION; GENE MUTATION; GENE SILENCING; HEAD AND NECK CANCER; HUMAN; METASTASIS; MICROARRAY ANALYSIS; NONHUMAN; PROTEIN EXPRESSION; PROTEOMICS; RADIOSENSITIVITY; REVIEW; SIGNAL TRANSDUCTION; SQUAMOUS CELL CARCINOMA; TUMOR MICROENVIRONMENT;

EID: 79953679881     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers3010415     Document Type: Review

References (80)

1. Parkin, D.M.; Bray, F.; Ferlay, J.; Pisani, P. Global cancer statistics, 2002. CA Cancer J. Clin. 2005, 55, 74-108.
2. Argiris, A.; Karamouzis, M.V.; Raben, D.; Ferris, R.L. Head and neck cancer. Lancet 2008, 371, 1695-1709.
3. Shackleton, M.; Quintana, E.; Fearon, E.R.; Morrison, S.J. Heterogeneity in cancer: Cancer stem cells versus clonal evolution. Cell 2009, 138, 822-829.
4. Dean, M.; Fojo, T.; Bates, S. Tumour stem cells and drug resistance. Nat. Rev. Cancer 2005, 5, 275-284.
5. Donnenberg, V.S.; Donnenberg, A.D. Multiple drug resistance in cancer revisited: The cancer stem cell hypothesis. J. Clin. Pharmaco. l 2005, 45, 872-877.
6. Wu, C.; Alman, B.A. Side population cells in human cancers. Cancer Lett. 2008, 268, 1-9.
7. Quintana, E.; Shackleton, M.; Foster, H.R.; Fullen, D.R.; Sabel, M.S.; Johnson, T.M.; Morrison, S.J. Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized. Cancer Cell 2010, 18, 510-523.
8. Gupta, P.B.; Chaffer, C.L.; Weinberg, R.A. Cancer stem cells: Mirage or reality? Nat. Med. 2009, 15, 1010-1012.
9. Lapidot, T.; Sirard, C.; Vormoor, J.; Murdoch, B.; Hoang, T.; Caceres-Cortes, J.; Minden, M.; Paterson, B.; Caligiuri, M.A.; Dick, J.E. A cell initiating human acute myeloid leukaemia after transplantation into scid mice. Nature 1994, 367, 645-648.
10. Al-Hajj, M.; Wicha, M.S.; Benito-Hernandez, A.; Morrison, S.J.; Clarke, M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 2003, 100, 3983-3988.
11. Collins, A.T.; Berry, P.A.; Hyde, C.; Stower, M.J.; Maitland, N.J. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005, 65, 10946-10951.
12. Curley, M.D.; Therrien, V.A.; Cummings, C.L.; Sergent, P.A.; Koulouris, C.R.; Friel, A.M.; Roberts, D.J.; Seiden, M.V.; Scadden, D.T.; Rueda, B.R.; Foster, R. Cd133 expression defines a tumor initiating cell population in primary human ovarian cancer. Stem Cells 2009, 27, 2875-2883.
13. Dalerba, P.; Dylla, S.J.; Park, I.K.; Liu, R.; Wang, X.; Cho, R.W.; Hoey, T.; Gurney, A.; Huang, E.H.; Simeone, D.M.; Shelton, A.A.; Parmiani, G.; Castelli, C.; Clarke, M.F. Phenotypic characterization of human colorectal cancer stem cells. Proc. Natl. Acad. Sci. USA 2007, 104, 10158-10163.
14. Hermann, P.C.; Huber, S.L.; Herrler, T.; Aicher, A.; Ellwart, J.W.; Guba, M.; Bruns, C.J.; Heeschen, C. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007, 1, 313-323.
15. Li, C.; Heidt, D.G.; Dalerba, P.; Burant, C.F.; Zhang, L.; Adsay, V.; Wicha, M.; Clarke, M.F.; Simeone, D.M. Identification of pancreatic cancer stem cells. Cancer Res. 2007, 67, 1030-1037.
16. O'Brien, C.A.; Pollett, A.; Gallinger, S.; Dick, J.E. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007, 445, 106-110.
17. Ricci-Vitiani, L.; Lombardi, D.G.; Pilozzi, E.; Biffoni, M.; Todaro, M.; Peschle, C.; De Maria, R. Identification and expansion of human colon-cancer-initiating cells. Nature 2007, 445, 111-115.
18. Singh, S.K.; Hawkins, C.; Clarke, I.D.; Squire, J.A.; Bayani, J.; Hide, T.; Henkelman, R.M.; Cusimano, M.D.; Dirks, P.B. Identification of human brain tumour initiating cells. Nature 2004, 432, 396-401.
19. Ma, I.; Allan, A.L. The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev. 2010, doi:10.1007/s12015-010-9208-4.
20. Reynolds, B.A.; Weiss, S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 1992, 255, 1707-1710.
21. Singh, S.K.; Clarke, I.D.; Terasaki, M.; Bonn, V.E.; Hawkins, C.; Squire, J.; Dirks, P.B. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003, 63, 5821-5828.
22. Okamoto, A.; Chikamatsu, K.; Sakakura, K.; Hatsushika, K.; Takahashi, G.; Masuyama, K. Expansion and characterization of cancer stem-like cells in squamous cell carcinoma of the head and neck. Oral Oncol. 2009, 45, 633-639.
23. Ito, Y.; Hamazaki, T.S.; Ohnuma, K.; Tamaki, K.; Asashima, M.; Okochi, H. Isolation of murine hair-inducing cells using the cell surface marker prominin-1/cd133. J. Invest. Dermatol. 2007, 127, 1052-1060.
24. Miraglia, S.; Godfrey, W.; Yin, A.H.; Atkins, K.; Warnke, R.; Holden, J.T.; Bray, R.A.; Waller, E.K.; Buck, D.W. A novel five-transmembrane hematopoietic stem cell antigen: Isolation, characterization, and molecular cloning. Blood 1997, 90, 5013-5021.
25. Uchida, N.; Buck, D.W.; He, D.; Reitsma, M.J.; Masek, M.; Phan, T.V.; Tsukamoto, A.S.; Gage, F.H.; Weissman, I.L. Direct isolation of human central nervous system stem cells. Proc. Natl. Acad. Sci. USA 2000, 97, 14720-14725.
26. Yin, A.H.; Miraglia, S.; Zanjani, E.D.; Almeida-Porada, G.; Ogawa, M.; Leary, A.G.; Olweus, J.; Kearney, J.; Buck, D.W. Ac133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997, 90, 5002-5012.
27. Zhang, Q.; Shi, S.; Yen, Y.; Brown, J.; Ta, J.Q.; Le, A.D. A subpopulation of cd133(+) cancer stem-like cells characterized in human oral squamous cell carcinoma confer resistance to chemotherapy. Cancer Lett. 2010, 289, 151-160.
28. Song, J.; Chang, I.; Chen, Z.; Kang, M.; Wang, C.Y. Characterization of side populations in hnscc: Highly invasive, chemoresistant and abnormal wnt signaling. PLoS One 2010, 5, e11456.
29. Ishizawa, K.; Rasheed, Z.A.; Karisch, R.; Wang, Q.; Kowalski, J.; Susky, E.; Pereira, K.; Karamboulas, C.; Moghal, N.; Rajeshkumar, N.V.; Hidalgo, M.; Tsao, M.; Ailles, L.; Waddell, T.K.; Maitra, A.; Neel, B.G.; Matsui, W. Tumor-initiating cells are rare in many human tumors. Cell Stem Cell 2010, 7, 279-282.
30. McKenzie, J.L.; Gan, O.I.; Doedens, M.; Dick, J.E. Human short-term repopulating stem cells are efficiently detected following intrafemoral transplantation into nod/scid recipients depleted of cd122+ cells. Blood 2005, 106, 1259-1261.
31. Monroe, M.M.; Anderson, E.C.; Clayburgh, D.R.; Wong, M.H. Cancer stem cells in head and neck squamous cell carcinoma. J. Oncol. 2011, Article ID 762780, doi:10.1155/2011/762780.
32. Prince, M.E.; Ailles, L.E. Cancer stem cells in head and neck squamous cell cancer. J. Clin. Oncol. 2008, 26, 2871-2875.
33. Chen, Z.G. The cancer stem cell concept in progression of head and neck cancer. J. Oncol. 2009, Article ID 894064, doi:10.1155/2009/894064.
34. Prince, M.E.; Sivanandan, R.; Kaczorowski, A.; Wolf, G.T.; Kaplan, M.J.; Dalerba, P.; Weissman, I.L.; Clarke, M.F.; Ailles, L.E. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc. Natl. Acad. Sci. USA 2007, 104, 973-978.
35. Ponta, H.; Sherman, L.; Herrlich, P.A. Cd44: From adhesion molecules to signalling regulators. Nat. Rev. Mol. Cell. Biol. 2003, 4, 33-45.
36. Gunthert, U.; Hofmann, M.; Rudy, W.; Reber, S.; Zoller, M.; Haussmann, I.; Matzku, S.; Wenzel, A.; Ponta, H.; Herrlich, P. A new variant of glycoprotein cd44 confers metastatic potential to rat carcinoma cells. Cell 1991, 65, 13-24.
37. Wang, S.J.; Wong, G.; de Heer, A.M.; Xia, W.; Bourguignon, L.Y. Cd44 variant isoforms in head and neck squamous cell carcinoma progression. Laryngoscope 2009, 119, 1518-1530.
38. Mack, B.; Gires, O. Cd44s and cd44v6 expression in head and neck epithelia. PLoS One 2008, 3, e3360.
39. Ginestier, C.; Hur, M.H.; Charafe-Jauffret, E.; Monville, F.; Dutcher, J.; Brown, M.; Jacquemier, J.; Viens, P.; Kleer, C.G.; Liu, S.; Schott, A.; Hayes, D.; Birnbaum, D.; Wicha, M.S.; Dontu, G. Aldh1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 2007, 1, 555-567.
40. Chen, Y.C.; Chen, Y.W.; Hsu, H.S.; Tseng, L.M.; Huang, P.I.; Lu, K.H.; Chen, D.T.; Tai, L.K.; Yung, M.C.; Chang, S.C.; Ku, H.H.; Chiou, S.H.; Lo, W.L. Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer. Biochem. Biophys. Res. Commun. 2009, 385, 307-313.
41. Clay, M.R.; Tabor, M.; Owen, J.H.; Carey, T.E.; Bradford, C.R.; Wolf, G.T.; Wicha, M.S.; Prince, M.E. Single-marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase. Head Neck 2010, 32, 1195-1201.
42. Krishnamurthy, S.; Dong, Z.; Vodopyanov, D.; Imai, A.; Helman, J.I.; Prince, M.E.; Wicha, M.S.; Nor, J.E. Endothelial cell-initiated signaling promotes the survival and self-renewal of cancer stem cells. Cancer Res. 2010, 70, 9969-9978.
43. Calabrese, C.; Poppleton, H.; Kocak, M.; Hogg, T.L.; Fuller, C.; Hamner, B.; Oh, E.Y.; Gaber, M.W.; Finklestein, D.; Allen, M.; Frank, A.; Bayazitov, I.T.; Zakharenko, S.S.; Gajjar, A.; Davidoff, A.; Gilbertson, R.J. A perivascular niche for brain tumor stem cells. Cancer Cell 2007, 11, 69-82.
44. Shen, Q.; Goderie, S.K.; Jin, L.; Karanth, N.; Sun, Y.; Abramova, N.; Vincent, P.; Pumiglia, K.; Temple, S. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 2004, 304, 1338-1340.
45. LaBarge, M.A. The difficulty of targeting cancer stem cell niches. Clin. Cancer. Res. 2010, 16, 3121-3129.
46. Moore, K.A.; Lemischka, I.R. Stem cells and their niches. Science 2006, 311, 1880-1885.
47. Wu, M.J.; Jan, C.I.; Tsay, Y.G.; Yu, Y.H.; Huang, C.Y.; Lin, S.C.; Liu, C.J.; Chen, Y.S.; Lo, J.F.; Yu, C.C. Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling. Mol. Cancer 2010, 9, 283.
48. Luo, S.; Mao, C.; Lee, B.; Lee, A.S. Grp78/bip is required for cell proliferation and protecting the inner cell mass from apoptosis during early mouse embryonic development. Mol. Cell. Biol. 2006, 26, 5688-5697.
49. Lee, E.; Nichols, P.; Spicer, D.; Groshen, S.; Yu, M.C.; Lee, A.S. Grp78 as a novel predictor of responsiveness to chemotherapy in breast cancer. Cancer Res. 2006, 66, 7849-7853.
50. Uramoto, H.; Sugio, K.; Oyama, T.; Nakata, S.; Ono, K.; Yoshimastu, T.; Morita, M.; Yasumoto, K. Expression of endoplasmic reticulum molecular chaperone grp78 in human lung cancer and its clinical significance. Lung Cancer 2005, 49, 55-62.
51. Chiu, C.C.; Lin, C.Y.; Lee, L.Y.; Chen, Y.J.; Kuo, T.F.; Chang, J.T.; Liao, C.T.; Wang, H.M.; Yen, T.C.; Shen, C.R.; Liao, S.K.; Cheng, A.J. Glucose-regulated protein 78 regulates multiple malignant phenotypes in head and neck cancer and may serve as a molecular target of therapeutic intervention. Mol. Cancer Ther. 2008, 7, 2788-2797.
52. Goodell, M.A.; Brose, K.; Paradis, G.; Conner, A.S.; Mulligan, R.C. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J. Exp. Med. 1996, 183, 1797-1806.
53. Wan, G.; Zhou, L.; Xie, M.; Chen, H.; Tian, J. Characterization of side population cells from laryngeal cancer cell lines. Head Neck 2010, 32, 1302-1309.
54. Loebinger, M.R.; Giangreco, A.; Groot, K.R.; Prichard, L.; Allen, K.; Simpson, C.; Bazley, L.; Navani, N.; Tibrewal, S.; Davies, D.; Janes, S.M. Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by abc transporter blockade. Br. J. Cancer 2008, 98, 380-387.
55. Zhang, P.; Zhang, Y.; Mao, L.; Zhang, Z.; Chen, W. Side population in oral squamous cell carcinoma possesses tumor stem cell phenotypes. Cancer Lett. 2009, 277, 227-234.
56. Belpomme, D.; Gauthier, S.; Pujade-Lauraine, E.; Facchini, T.; Goudier, M.J.; Krakowski, I.; Netter-Pinon, G.; Frenay, M.; Gousset, C.; Marie, F.N.; Benmiloud, M.; Sturtz, F. Verapamil increases the survival of patients with anthracycline-resistant metastatic breast carcinoma. Ann. Oncol. 2000, 11, 1471-1476.
57. List, A.F.; Kopecky, K.J.; Willman, C.L.; Head, D.R.; Persons, D.L.; Slovak, M.L.; Dorr, R.; Karanes, C.; Hynes, H.E.; Doroshow, J.H.; Shurafa, M.; Appelbaum, F.R. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: A southwest oncology group study. Blood 2001, 98, 3212-3220.
58. Sonneveld, P.; Suciu, S.; Weijermans, P.; Beksac, M.; Neuwirtova, R.; Solbu, G.; Lokhorst, H.; van der Lelie, J.; Dohner, H.; Gerhartz, H.; Segeren, C.M.; Willemze, R.; Lowenberg, B. Cyclosporin a combined with vincristine, doxorubicin and dexamethasone (vad) compared with vad alone in patients with advanced refractory multiple myeloma: An eortc-hovon randomized phase iii study (06914). Br. J. Haematol. 2001, 115, 895-902.
59. Bao, S.; Wu, Q.; McLendon, R.E.; Hao, Y.; Shi, Q.; Hjelmeland, A.B.; Dewhirst, M.W.; Bigner, D.D.; Rich, J.N. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006, 444, 756-760.
60. Diehn, M.; Cho, R.W.; Lobo, N.A.; Kalisky, T.; Dorie, M.J.; Kulp, A.N.; Qian, D.; Lam, J.S.; Ailles, L.E.; Wong, M.; Joshua, B.; Kaplan, M.J.; Wapnir, I.; Dirbas, F.M.; Somlo, G.; Garberoglio, C.; Paz, B.; Shen, J.; Lau, S.K.; Quake, S.R.; Brown, J.M.; Weissman, I.L.; Clarke, M.F. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 2009, 458, 780-783.
61. Lo, W.L.; Kao, S.Y.; Chi, L.Y.; Wong, Y.K.; Chang, R.C. Outcomes of oral squamous cell carcinoma in taiwan after surgical therapy: Factors affecting survival. J. Oral. Maxillofac. Surg. 2003, 61, 751-758.
62. 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, 744-749.
63. Pro, B.; Dang, N.H. Cd26/dipeptidyl peptidase iv and its role in cancer. Histol. Histopathol. 2004, 19, 1345-1351.
64. Pang, R.; Law, W.L.; Chu, A.C.; Poon, J.T.; Lam, C.S.; Chow, A.K.; Ng, L.; Cheung, L.W.; Lan, X.R.; Lan, H.Y.; Tan, V.P.; Yau, T.C.; Poon, R.T.; Wong, B.C. A subpopulation of cd26+ cancer stem cells with metastatic capacity in human colorectal cancer. Cell Stem Cell 6, 603-615.
65. Thiery, J.P.; Acloque, H.; Huang, R.Y.; Nieto, M.A. Epithelial-mesenchymal transitions in development and disease. Cell 2009, 139, 871-890.
66. Mani, S.A.; Guo, W.; Liao, M.J.; Eaton, E.N.; Ayyanan, A.; Zhou, A.Y.; Brooks, M.; Reinhard, F.; Zhang, C.C.; Shipitsin, M.; Campbell, L.L.; Polyak, K.; Brisken, C.; Yang, J.; Weinberg, R.A. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008, 133, 704-715.
67. Wellner, U.; Schubert, J.; Burk, U.C.; Schmalhofer, O.; Zhu, F.; Sonntag, A.; Waldvogel, B.; Vannier, C.; Darling, D.; zur Hausen, A.; Brunton, V.G.; Morton, J.; Sansom, O.; Schuler, J.; Stemmler, M.P.; Herzberger, C.; Hopt, U.; Keck, T.; Brabletz, S.; Brabletz, T. The emt-activator zeb1 promotes tumorigenicity by repressing stemness-inhibiting micrornas. Nat. Cell Biol. 2009, 11, 1487-1495.
68. Batlle, E.; Sancho, E.; Franci, C.; Dominguez, D.; Monfar, M.; Baulida, J.; Garcia De Herreros, A. The transcription factor snail is a repressor of e-cadherin gene expression in epithelial tumour cells. Nat. Cell Biol. 2000, 2, 84-89.
69. Zhou, B.P.; Deng, J.; Xia, W.; Xu, J.; Li, Y.M.; Gunduz, M.; Hung, M.C. Dual regulation of snail by gsk-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat. Cell Biol. 2004, 6, 931-940.
70. Molofsky, A.V.; Pardal, R.; Iwashita, T.; Park, I.K.; Clarke, M.F.; Morrison, S.J. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 2003, 425, 962-967.
71. Park, I.K.; Qian, D.; Kiel, M.; Becker, M.W.; Pihalja, M.; Weissman, I.L.; Morrison, S.J.; Clarke, M.F. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 2003, 423, 302-305.
72. Sangiorgi, E.; Capecchi, M.R. Bmi1 is expressed in vivo in intestinal stem cells. Nat. Genet. 2008, 40, 915-920.
73. Widschwendter, M.; Fiegl, H.; Egle, D.; Mueller-Holzner, E.; Spizzo, G.; Marth, C.; Weisenberger, D.J.; Campan, M.; Young, J.; Jacobs, I.; Laird, P.W. Epigenetic stem cell signature in cancer. Nat. Genet. 2007, 39, 157-158.
74. Brunner, M.; Thurnher, D.; Pammer, J.; Geleff, S.; Heiduschka, G.; Reinisch, C.M.; Petzelbauer, P.; Erovic, B.M. Expression of vegf-a/c, vegf-r2, pdgf-alpha/beta, c-kit, egfr, her-2/neu, mcl-1 and bmi-1 in merkel cell carcinoma. Mod. Pathol. 2008, 21, 876-884.
75. Yu, C.C.; Lo, W.L.; Chen, Y.W.; Huang, P.I.; Hsu, H.S.; Tseng, L.M.; Hung, S.C.; Kao, S.Y.; Chang, C.J.; Chiou, S.H. Bmi-1 regulates snail expression and promotes metastasis ability in head and neck squamous cancer-derived aldh1 positive cells. J. Oncol. 2011, Article ID 609259, doi:10.1155/2011/609259.
76. Yang, M.H.; Hsu, D.S.; Wang, H.W.; Wang, H.J.; Lan, H.Y.; Yang, W.H.; Huang, C.H.; Kao, S.Y.; Tzeng, C.H.; Tai, S.K.; Chang, S.Y.; Lee, O.K.; Wu, K.J. Bmi1 is essential in twist1-induced epithelial-mesenchymal transition. Nat. Cell Biol. 2010, 12, 982-992.
77. Chenn, A.; Walsh, C.A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 2002, 297, 365-369.
78. Sato, N.; Meijer, L.; Skaltsounis, L.; Greengard, P.; Brivanlou, A.H. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of wnt signaling by a pharmacological gsk-3-specific inhibitor. Nat. Med. 2004, 10, 55-63.
79. Zechner, D.; Fujita, Y.; Hulsken, J.; Muller, T.; Walther, I.; Taketo, M.M.; Crenshaw, E.B., 3rd; Birchmeier, W.; Birchmeier, C. Beta-catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system. Dev. Biol. 2003, 258, 406-418.
80. Takahashi-Yanaga, F.; Kahn, M. Targeting wnt signaling: Can we safely eradicate cancer stem cells? Clin. Cancer Res. 2010, 16, 3153-3162.