RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer
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 c...
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MDPI AG
2021-06-01
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Series: | Cancers |
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Online Access: | https://www.mdpi.com/2072-6694/13/13/3192 |
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author | Antoine Gleizes Mouna Triki Sandrine Bonnet Naomi Baccari Gabriel Jimenez-Dominguez Aurélie Covinhes Nelly Pirot Philippe Blache Rong Yuan Balázs Győrffy Vincent Cavaillès Marion Lapierre |
author_facet | Antoine Gleizes Mouna Triki Sandrine Bonnet Naomi Baccari Gabriel Jimenez-Dominguez Aurélie Covinhes Nelly Pirot Philippe Blache Rong Yuan Balázs Győrffy Vincent Cavaillès Marion Lapierre |
author_sort | Antoine Gleizes |
collection | DOAJ |
description | 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. |
first_indexed | 2024-03-09T04:53:03Z |
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id | doaj.art-6d96531db0d14b3594f321d97b3433fb |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-09T04:53:03Z |
publishDate | 2021-06-01 |
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series | Cancers |
spelling | doaj.art-6d96531db0d14b3594f321d97b3433fb2023-12-03T13:08:20ZengMDPI AGCancers2072-66942021-06-011313319210.3390/cancers13133192RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal CancerAntoine Gleizes0Mouna Triki1Sandrine Bonnet2Naomi Baccari3Gabriel Jimenez-Dominguez4Aurélie Covinhes5Nelly Pirot6Philippe Blache7Rong Yuan8Balázs Győrffy9Vincent Cavaillès10Marion Lapierre11IRCM—Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier, CNRS, 208 rue des Apothicaires, F-34298 Montpellier, FranceIRCM—Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier, CNRS, 208 rue des Apothicaires, F-34298 Montpellier, FranceIRCM—Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier, CNRS, 208 rue des Apothicaires, F-34298 Montpellier, FranceIRCM—Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier, CNRS, 208 rue des Apothicaires, F-34298 Montpellier, FranceIRCM—Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier, CNRS, 208 rue des Apothicaires, F-34298 Montpellier, FranceBioCampus, RHEM, Université de Montpellier, CNRS, INSERM, F-34093 Montpellier, FranceBioCampus, RHEM, Université de Montpellier, CNRS, INSERM, F-34093 Montpellier, FranceIRCM—Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier, CNRS, 208 rue des Apothicaires, F-34298 Montpellier, FranceDepartment of Medical Microbiology, Immunology and Cell Biology, School of Medicine, Southern Illinois University, Springfield, IL 62794-9628, USADepartment of Bioinformatics, Semmelweis University, 1094 Budapest, HungaryIRCM—Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier, CNRS, 208 rue des Apothicaires, F-34298 Montpellier, FranceIRCM—Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier, CNRS, 208 rue des Apothicaires, F-34298 Montpellier, FranceRIP140 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.https://www.mdpi.com/2072-6694/13/13/3192intestinal epitheliumcell differentiationcolon cancerRIP140SOX9transcriptional regulation |
spellingShingle | Antoine Gleizes Mouna Triki Sandrine Bonnet Naomi Baccari Gabriel Jimenez-Dominguez Aurélie Covinhes Nelly Pirot Philippe Blache Rong Yuan Balázs Győrffy Vincent Cavaillès Marion Lapierre RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer Cancers intestinal epithelium cell differentiation colon cancer RIP140 SOX9 transcriptional regulation |
title | RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer |
title_full | RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer |
title_fullStr | RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer |
title_full_unstemmed | RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer |
title_short | RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer |
title_sort | rip140 represses intestinal paneth cell differentiation and interplays with sox9 signaling in colorectal cancer |
topic | intestinal epithelium cell differentiation colon cancer RIP140 SOX9 transcriptional regulation |
url | https://www.mdpi.com/2072-6694/13/13/3192 |
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