| Added by | mollevi |
|---|---|
| Last modified by | ircm doc |
| Group name | EquipeVC |
| Item Type | Journal Article |
| Title | RIP140 increases APC expression and controls intestinal homeostasis and tumorigenesis |
| Creator | Lapierre et al. |
| Author | M. Lapierre |
| Author | S. Bonnet |
| Author | C. Bascoul-Mollevi |
| Author | I. Ait-Arsa |
| Author | S. Jalaguier |
| Author | M. Del Rio |
| Author | M. Plateroti |
| Author | P. Roepman |
| Author | M. Ychou |
| Author | J. Pannequin |
| Author | F. Hollande |
| Author | M. Parker |
| Author | V. Cavailles |
| Abstract | Deregulation of the Wnt/APC/beta-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 beta-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. |
| Publication | J Clin Invest |
| Volume | 124 |
| Pages | 1899-913 |
| Date | May 2014 |
| Journal Abbr | The Journal of clinical investigation |
| DOI | 10.1172/JCI65178 |
| ISSN | 1558-8238 (Electronic) 0021-9738 (Linking) |
| Tags | *Gene Expression Regulation, Neoplastic, *Homeostasis, Adaptor Proteins, Signal Transducing/genetics/*metabolism, Adenomatous Polyposis Coli Protein/*biosynthesis/genetics, Animals, Apoptosis/genetics, Cell Line, Tumor, Cell Proliferation, Cell Transformation, Neoplastic/genetics/*metabolism/pathology, Colonic Neoplasms/*metabolism/pathology, Epithelial Cells/*metabolism/pathology, Female, Heterografts, Humans, Intestinal Mucosa/*metabolism/pathology, Male, Mice, Mice, Knockout, Mice, Nude, Neoplasm Transplantation, Nuclear Proteins/genetics/*metabolism, original, own, top |
| Date Added | 2018/11/14 - 12:10:52 |
| Date Modified | 2025/01/09 - 15:26:41 |
| Notes and Attachments | (Note) (Note) 24667635 (Attachment) |
Institut de Recherche en Cancérologie de
