Transcriptional regulation of the intestinal nuclear bile acid farnesoid X receptor (FXR) by the caudal-related homeobox 2 (CDX2).
Fiche publication
Date publication
octobre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FREUND Jean-Noël, Dr GROSS Isabelle
Tous les auteurs :
Modica S, Cariello M, Morgano A, Gross I, Vegliante MC, Murzilli S, Salvatore L, Freund JN, Sabba C, Moschetta A
Lien Pubmed
Résumé
Farnesoid X receptor (FXR, NR1H4) is a bile acid-activated transcription factor that belongs to the nuclear receptor superfamily. It is highly expressed in the enterohepatic system, where it senses bile acid levels to consequently reduce their synthesis while inducing their detoxification. Bile acids are intestinal tumor promoters and their concentrations have to be tightly regulated. Indeed, reduced expression of FXR in the intestine increases colorectal cancer susceptibility in mice, whereas its activation can promote apoptosis in genetically modified cells. Notably, despite the broad knowledge of the FXR enterohepatic transcriptional activity, the molecular mechanisms regulating FXR expression in the intestine are still unknown. Herein, by combining both gain and loss of function approaches and FXR promoter activity studies, we identified caudal-related homeobox 2 (CDX2) transcription factor as a positive regulator of FXR expression in the enterocytes. Our results provide a putative novel tool for modulating FXR expression against bile acid-related colorectal cancer progression.
Référence
J Biol Chem. 2014 Oct 10;289(41):28421-32