RIP140 increases APC expression and controls intestinal homeostasis and tumorigenesis. - Archive ouverte HAL Access content directly
Journal Articles Journal of Clinical Investigation Year : 2014

RIP140 increases APC expression and controls intestinal homeostasis and tumorigenesis.

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Paul Roepman
  • Function : Author
Julie Pannequin

Abstract

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.
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Dates and versions

inserm-00972586 , version 1 (03-04-2014)

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Marion Lapierre, Sandrine Bonnet, Caroline Bascoul-Mollevi, Imade Ait-Arsa, Stéphan Jalaguier, et al.. RIP140 increases APC expression and controls intestinal homeostasis and tumorigenesis.. Journal of Clinical Investigation, 2014, 124 (5), pp.1899-913. ⟨10.1172/JCI65178⟩. ⟨inserm-00972586⟩
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