RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer

Gleizes, Antoine; Triki, Mouna; Bonnet, Sandrine; Baccari, Naomi; Jiménez-Domínguez, Gabriel; Covinhes, Aurélie; Pirot, Nelly; Blache, Philippe; Yuan, Rong; Győrffy, Balázs; Cavaillès, Vincent; Lapierre, Marion

doi:10.3390/cancers13133192

Cited by 4 publications

(2 citation statements)

References 54 publications

(72 reference statements)

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“…In the intestinal epithelium, our laboratory demonstrated that RIP140 inhibits the Wnt/β-catenin signaling pathway and, as a consequence, exerts an anti-proliferative effect [ 24 ] . In line with this result, we found that this transcription coregulator inhibits the Paneth cells lineage through the regulation of SOX9 expression and activity [ 25 ] . In addition, RIP140 expression decreased in CRC samples compared to the adjacent healthy tissue.…”

Section: Introductionmentioning

confidence: 63%

RIP140 regulates POLK gene expression and the response to alkylating drugs in colon cancer cells

Palassin¹,

Lapierre²,

Bonnet³

et al. 2022

Cancer Drug Resist

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Aim: The transcription factor RIP140 (receptor interacting protein of 140 kDa) is involved in intestinal tumorigenesis. It plays a role in the control of microsatellite instability (MSI), through the regulation of MSH2 and MSH6 gene expression. The aim of this study was to explore its effect on the expression of POLK, the gene encoding the specialized translesion synthesis (TLS) DNA polymerase κ known to perform accurate DNA synthesis at microsatellites. Methods: Different mouse models and engineered human colorectal cancer (CRC) cell lines were used to analyze by RT-qPCR, while Western blotting and luciferase assays were used to elucidate the role of RIP140 on POLK gene expression. Published DNA microarray datasets were reanalyzed. The in vitro sensitivity of CRC cells to methyl methane sulfonate and cisplatin was determined. Results: RIP140 positively regulates, at the transcriptional level, the expression of the POLK gene, and this effect involves, at least partly, the p53 tumor suppressor. In different cohorts of CRC biopsies (with or without MSI), a strong positive correlation was observed between RIP140 and POLK gene expression. In connection with its effect on POLK levels and the TLS function of this polymerase, the cellular response to methyl methane sulfonate was increased in cells lacking the Rip140 gene. Finally, the association of RIP140 expression with better overall survival of CRC patients was observed only when the corresponding tumors exhibited low levels of POLK, thus strengthening the functional link between the two genes in human CRC. Conclusion: The regulation of POLK gene expression by RIP140 could thus contribute to the maintenance of microsatellite stability, and more generally to the control of genome integrity.

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Section: Introductionmentioning

confidence: 63%

RIP140 regulates POLK gene expression and the response to alkylating drugs in colon cancer cells

Palassin¹,

Lapierre²,

Bonnet³

et al. 2022

Cancer Drug Resist

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“…PCs are highly specific cells of the small intestine, located within Lieberkühn crypts in a pyramidal shape ( Paneth, 1887 ). Under normal conditions, PCs are located all along the entire length of the small intestine, but under disease conditions, they may also be found in the esophagus and colon ( Chen et al, 2015 ; Singh et al, 2020 ; Gleizes et al, 2021 ). PCs first appear at 13.5 weeks of gestation, and at this point, their density is very low ( Stanford et al, 2020 ).…”

Section: The Characteristics and Biological Role Of Pcmentioning

confidence: 99%

Paneth cell development in the neonatal gut: pathway regulation, development, and relevance to necrotizing enterocolitis

Yang

Shi

2023

Front. Cell Dev. Biol.

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Paneth cells (PCs) are intestinal epithelial cells (IECs) that contain eosinophilic granules, which are located in Lieberkühn crypts. An increasing number of animal and human experiments have indicated that PCs are involved in the progression of a variety of intestinal as well as systemic inflammatory responses including necrotizing enterocolitis (NEC). NEC is an enteric acquired disease with high mortality that usually occurs in premature infants and neonates, however the underlying mechanisms remain unclear. In this review, we summarize the features of PCs, including their immune function, association with gut microbiota and intestinal stem cells, and their mechanism of regulating IEC death to explore the possible mechanisms by which PCs affect NEC.

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RIP140 regulates transcription factor HES1 oscillatory expression and mitogenic activity in colon cancer cells

Sfeir,

Kajdan,

Jalaguier

et al. 2024

Molecular Oncology

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The transcription factor receptor‐interacting protein 140 (RIP140) regulates intestinal homeostasis and tumorigenesis through Wnt signaling. In this study, we investigated its effect on the Notch/HES1 signaling pathway. In colorectal cancer (CRC) cell lines, RIP140 positively regulated HES1 gene expression at the transcriptional level via a recombining binding protein suppressor of hairless (RBPJ)/neurogenic locus notch homolog protein 1 (NICD)‐mediated mechanism. In support of these in vitro data, RIP140 and HES1 expression significantly correlated in mouse intestine and in a cohort of CRC samples, thus supporting the positive regulation of HES1 gene expression by RIP140. Interestingly, when the Notch pathway is fully activated, RIP140 exerted a strong inhibition of HES1 gene transcription controlled by the level of HES1 itself. Moreover, RIP140 directly interacts with HES1 and reversed its mitogenic activity in human CRC cells. In line with this observation, HES1 levels were associated with a better patient survival only when tumors expressed high levels of RIP140. Our data identify RIP140 as a key regulator of the Notch/HES1 signaling pathway, with a dual effect on HES1 gene expression at the transcriptional level and a strong impact on colon cancer cell proliferation.

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RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer

Cited by 4 publications

References 54 publications

RIP140 regulates POLK gene expression and the response to alkylating drugs in colon cancer cells

RIP140 regulates POLK gene expression and the response to alkylating drugs in colon cancer cells

Paneth cell development in the neonatal gut: pathway regulation, development, and relevance to necrotizing enterocolitis

RIP140 regulates transcription factor HES1 oscillatory expression and mitogenic activity in colon cancer cells

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