RIP140 increases APC expression and controls intestinal homeostasis and tumorigenesis
| Autor: | Stéphan Jalaguier, Michela Plateroti, Frédéric Hollande, Caroline Bascoul-Mollevi, Marion Lapierre, Imade Ait-Arsa, Paul Roepman, Maguy Del Rio, Vincent Cavaillès, Marc Ychou, Malcolm G. Parker, Sandrine Bonnet, Julie Pannequin |
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| Přispěvatelé: | Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Unité de biostatistiques, CRLCC Val d'Aurelle - Paul Lamarque, Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Agendia NV, Agendia NV, Amsterdam, Agendia Inc, Irvine, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institute of Reproductive and Developmental Biology (IRDB), Imperial College London, This work was supported by INSERM, Université de Montpellier 1, Fondation Lejeune, INCa (2011-054), SIRIC Montpellier and the Institut régional du Cancer de Montpellier (ICM). |
| Rok vydání: | 2014 |
| Předmět: |
Male
Colorectal cancer Adenomatous Polyposis Coli Protein Mice Nude [SDV.CAN]Life Sciences [q-bio]/Cancer Apoptosis Biology medicine.disease_cause Mice Intestinal mucosa Cell Line Tumor medicine Animals Homeostasis Humans Intestinal Mucosa Adaptor Proteins Signal Transducing Cell Proliferation Mice Knockout Regulation of gene expression Cell growth Wnt signaling pathway Nuclear Proteins Epithelial Cells General Medicine medicine.disease Nuclear Receptor Interacting Protein 1 3. Good health Gene Expression Regulation Neoplastic Cell Transformation Neoplastic Colonic Neoplasms Immunology Cancer research Heterografts Female Signal transduction Carcinogenesis Neoplasm Transplantation Research Article |
| Zdroj: | Journal of Clinical Investigation Journal of Clinical Investigation, American Society for Clinical Investigation, 2014, 124 (5), pp.1899-913. ⟨10.1172/JCI65178⟩ |
| ISSN: | 0021-9738 |
| Popis: | International audience; Deregulation of the Wnt/APC/β-catenin signaling pathway is an important consequence of tumor suppressor APC dysfunction. Genetic and molecular data have established that disruption of this pathway contributes to the development of colorectal cancer. Here, we demonstrate that the transcriptional coregulator RIP140 regulates intestinal homeostasis and tumorigenesis. Using Rip140-null mice and mice overexpressing human RIP140, we found that RIP140 inhibited intestinal epithelial cell proliferation and apoptosis. Interestingly, following whole-body irradiation, mice lacking RIP140 exhibited improved regenerative capacity in the intestine, while mice overexpressing RIP140 displayed reduced recovery. Enhanced RIP140 expression strongly repressed human colon cancer cell proliferation in vitro and after grafting onto nude mice. Moreover, in murine tissues and human cancer cells, RIP140 stimulated APC transcription and inhibited β-catenin activation and target gene expression. Finally, RIP140 mRNA and RIP140 protein levels were decreased in human colon cancers compared with those in normal mucosal tissue, and low levels of RIP140 expression in adenocarcinomas from patients correlated with poor prognosis. Together, these results support a tumor suppressor role for RIP140 in colon cancer. |
| Databáze: | OpenAIRE |
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