| Title: |
RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer |
| Authors: |
Gleizes, Antoine; Triki, Mouna; Bonnet, Sandrine; Baccari, Naomi; Jimenez-Dominguez, Gabriel; Covinhes, Aurélie; Cavaillès, Vincent; Blache, Philippe; Yuan, Rong; Győrffy, Balázs; Lapierre, Marion |
| Contributors: |
Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM); CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM); BioCampus (BCM); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS); Southern Illinois University Carbondale (SIU); Semmelweis University Budapest; Research Centre for Natural Sciences; Hungarian Academy of Sciences (MTA) |
| Source: |
ISSN: 2072-6694. |
| Publisher Information: |
CCSD; MDPI |
| Publication Year: |
2021 |
| Collection: |
Université de Montpellier: HAL |
| Subject Terms: |
intestinal epithelium; cell differentiation; colon cancer; RIP140; SOX9; transcriptional regulation; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; RIP140 is a major transcriptional coregulator of gut homeostasis and tumorigenesis through the regulation of Wnt/APC signaling. Here, we investigated the effect of RIP140 on Paneth cell differentiation and its interplay with the transcription factor SOX9. Using loss of function mouse models, human colon cancer cells, and tumor microarray data sets we evaluated the role of RIP140 in SOX9 expression and activity using RT-qPCR, immunohistochemistry, luciferase reporter assays, and GST-pull down. We first evidence that RIP140 strongly represses the Paneth cell lineage in the intestinal epithelium cells by inhibiting Sox9 expression. We then demonstrate that RIP140 interacts with SOX9 and inhibits its transcriptional activity. Our results reveal that the Wnt signaling pathway exerts an opposite regulation on SOX9 and RIP140. Finally, the levels of expression of RIP140 and SOX9 exhibit a reverse response and prognosis value in human colorectal cancer biopsies. This work highlights an intimate transcriptional cross-talk between RIP140 and SOX9 in intestinal physiopathology. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.3390/cancers13133192 |
| Availability: |
https://hal.science/hal-03358555; https://hal.science/hal-03358555v1/document; https://hal.science/hal-03358555v1/file/cancers-13-03192.pdf; https://doi.org/10.3390/cancers13133192 |
| Rights: |
http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.15B677F2 |
| Database: |
BASE |