Research Article
Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion
Article first published online: 27 AUG 2009
DOI: 10.1002/emmm.200900039
Copyright © 2009 EMBO Molecular Medicine
This is an Open Access article under the terms of the Creative Commons Attribution Non Commercial License which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Additional Information
How to Cite
Varnat, F., Duquet, A., Malerba, M., Zbinden, M., Mas, C., Gervaz, P. and Ruiz i Altaba, A. (2009), Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med, 1: 338–351. doi: 10.1002/emmm.200900039
Publication History
- Issue published online: 28 SEP 2009
- Article first published online: 27 AUG 2009
- Manuscript Accepted: 14 JUL 2009
- Manuscript Revised: 9 JUL 2009
- Manuscript Received: 15 JUN 2009
References
- , , , , , , , (2006) Gli1, downregulated in colorectal cancers, inhibits proliferation of colon cancer cells involving Wnt signalling activation. Gut 55: 991-999
- , , , , , , , , (2009) Hedgehog signaling is involved in differentiation of normal colonic tissue rather than in tumor proliferation. Virchows Arch 454: 369-379
- , , , , , , (2000) The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2: 84-89
- , , , , , , , , , , et al (2003) Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 425: 846-851
- , , , , , (2007) Sonic hedgehog-Gli1 pathway in colorectal adenocarcinomas. World J Gastroenterol 13: 1659-1665
- , , , , , , , (2000) The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2: 76-83
- , , , , , , (2007) Hedgehog signaling pathway is inactive in colorectal cancer cell lines. Int J Canc 121: 2622-2627 Direct Link:
- , , , , (2007) HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 17: 165-172
- , , , (1998) Teratogen-mediated inhibition of target tissue response to Shh signaling. Science 280: 1603-1607
- , , , , (1997) Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours. Nature 389: 876-881
- , , , , , , , (2001) The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. Development 128: 5201-5212
- , , , , , , , , , (2006) Sonic Hedgehog-dependent proliferation in a series of patients with colorectal cancer. Surgery 139: 665-670
- , , , , , , , , , , et al (2006) Smoothened gene mutations found in digestive cancer have no aberrant Hedgehog signaling activity. J Gastroenterol 41: 1238-1239
- , , , , , , , , , (2008) Biological and genetic characteristics of tumor-initiating cells in colon cancer. Ann Surg Oncol 15: 638-648
- , , , (1998) The teratogenic Veratrum alkaloid cyclopamine inhibits sonic hedgehog signal transduction. Development 125: 3553-3562
- (1970) Teratogenic compounds of Veratrum californicum (Durand) X. Cyclopia in rabbits produced by cyclopamine. Teratology 3: 175-180 Direct Link:
- (1978) Cyclopamine and related steroidal alkaloid teratogens: their occurrence, structural relationship, and biologic effects. Lipids 13: 708-715
- , , , , , , (2006) Snail induction is an early response to Gli1 that determines the efficiency of epithelial transformation. Oncogene 25: 609-621
- , , , , , (2005) Epithelial hedgehog signals pattern the intestinal crypt-villus axis. Development 132: 279-289
- , , , , , , , , (2006) Sonic hedgehog mRNA expression by real-time quantitative PCR in normal and tumor tissues from colorectal cancer patients. Canc Lett 233: 117-123
- , , , , , , (1997) Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275: 1787-1790
- , , , (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445: 106-110
- , , , , , (2004) Expression of Sonic hedgehog pathway genes is altered in colonic neoplasia. J Pathol 203: 909-917 Direct Link:
- , (2004) Hedgehog-GLI signaling regulates the behavior of cells with stem cell properties in the developing neocortex. Development 131: 337-345
- , , , , , , , , , , et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321: 1807-1812
- , , (2004) Sonic hedgehog-patched Gli signaling in the developing rat prostate gland: lobe-specific suppression by neonatal estrogens reduces ductal growth and branching. Dev Biol 273: 257-275
- , , , , (2004) Hedgehog signaling in colorectal tumour cells: induction of apoptosis with cyclopamine treatment. Int J Canc 110: 831-837 Direct Link:
- , , , , , , (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445: 111-115
- (1999) Gli proteins encode context-dependent positive and negative functions: implications for development and disease. Development 126: 3205-3216
- (2008) Therapeutic inhibition of Hedgeog-GLI signaling in cancer: Epithelial, stromal or stem cell targets? Canc Cell 14: 281-283
- , , (2007) The Gli code: an information nexus regulating cell fate, stemness and cancer. Trends Cell Biol 17: 438-447
- , , , , , , , , , (2004) Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc Natl Acad Sci USA 101: 12561-12566
- , (2005) In vivo inhibition of endogenous brain tumors through systemic interference with Hedgehog signaling in mice. Mech Dev 122: 223-230
- , , , , , , , , , , et al (2008) CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J Clin Invest 118: 2111-2120
- , , , , , , (2009) Prominin-1/CD133 marks stem cells and early progenitors in mouse small intestine. Gastroenterology 136: 2187-2194
- , , , , , , , (2007) Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways. Proc Natl Acad Sci USA 104: 5895-5900
- , (2009) A GLI1-p53 inhibitory loop regulates neural stem cell and tumor cell numbers. EMBO J 28: 663-679
- , , , , , , (2009) Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis. Proc Natl Acad Sci USA 106: 4254-4259
- , , , , , , , , , , et al (2007) Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 1: 389-402
- , , , , , , , , , , et al (2002) The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111: 241-250
- , , , , , , , , , , et al (2004) Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation. Nat Genet 36: 277-282
- , , , , , , , , (2008) Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci USA 105: 13427-13432
- , , , , , , , , , , et al (2007) The genomic landscapes of human breast and colorectal cancers. Science 318: 1108-1113
- , , , , , , , , , , et al (2008) A paracrine requirement for hedgehog signalling in cancer. Nature 455: 406-410
- , , , , , , , , , (2009) Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 457: 603-607

1757-4684/asset/olbannerleft.jpg?v=1&s=bbd2e0b80f5732e6debc8359b97d6dd36437820d)
1757-4684/asset/olbannerright.jpg?v=1&s=b2a7dc2c527cdc2509c695006f69ea9f80aaab1a)
1757-4684/asset/cover.gif?v=1&s=f0ae6ba1c75dc3c8ab91b28fcfb5cf75613dca6f)