The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells
| Autor: | Marc van de Wetering, Petra Moerer, Hans Clevers, Steven T. Pals, Anna-Pavlina G. Haramis, Damien Coudreuse, Cornelis Verweij, Menno Tjon-Pon-Fong, Irma Oving, Wim de Lau, Martin Eilers, Gwen Soete, Maaike van den Born, Elena Sancho, Adam Hurlstone, Karin van der Horn, René H. Medema, Eduard Batlle |
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| Přispěvatelé: | Pathology, Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Beta-catenin Cellular differentiation TCF/LEF family General Biochemistry Genetics and Molecular Biology Geneeskunde Proto-Oncogene Proteins c-myc Transactivation Cyclin D1 Cyclins Gene expression Tumor Cells Cultured Humans Intestinal Mucosa beta Catenin biology Biochemistry Genetics and Molecular Biology(all) Cell Cycle Wnt signaling pathway Cell Differentiation Cell cycle Molecular biology DNA-Binding Proteins Cytoskeletal Proteins Cell Transformation Neoplastic Phenotype biology.protein Cancer research Trans-Activators Colorectal Neoplasms TCF Transcription Factors Transcription Factor 7-Like 2 Protein Cell Division Transcription Factors |
| Zdroj: | BASE-Bielefeld Academic Search Engine Cell, 111(2), 241-250. Cell Press Cell, 111, 241-250. Elsevier B.V. Cell, 111(2), 241. Elsevier |
| ISSN: | 0092-8674 |
| Popis: | The transactivation of TCF target genes induced by Writ pathway mutations constitutes the primary transforming event in colorectal cancer (CRC). We show that disruption of beta-catenin/TCF-4 activity in CRC cells induces a rapid G1 arrest and blocks a genetic program that is physiologically active in the proliferative compartment of colon crypts. Coincidently, an intestinal differentiation program is induced. The TCF-4 target gene c-MYC plays a central role in this switch by direct repression of the p21(CIP1/WAF1) promoter. Following disruption of beta-catenin/TCF-4 activity, the decreased expression of c-MYC releases p21(CIP1/WAF1), transcription, which in turn mediates G1 arrest and differentiation. Thus, the beta-catenin/TCF-4 complex constitutes the master switch that controls proliferation versus differentiation in healthy and malignant intestinal epithelial cells |
| Databáze: | OpenAIRE |
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