TY - JOUR
T1 - Transcriptional regulation of the intestinal nuclear bile acid Farnesoid X Receptor (FXR) by the caudal-related homeobox 2 (CDX2)
AU - Modica, Salvatore
AU - Cariello, Marica
AU - Morgano, Annalisa
AU - Gross, Isabelle
AU - Vegliante, Maria Carmela
AU - Murzilli, Stefania
AU - Salvatore, Lorena
AU - Freund, Jean Noel
AU - Sabbà, Carlo
AU - Moschetta, Antonio
N1 - Publisher Copyright:
© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2014/10/10
Y1 - 2014/10/10
N2 - Farnesoid X receptor (FXR, NR1H4) is a bile acid-activated transcription factor that belongs to the nuclear receptor super-family. 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.
AB - Farnesoid X receptor (FXR, NR1H4) is a bile acid-activated transcription factor that belongs to the nuclear receptor super-family. 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.
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U2 - 10.1074/jbc.M114.571513
DO - 10.1074/jbc.M114.571513
M3 - Article
C2 - 25138215
AN - SCOPUS:84907637331
SN - 0021-9258
VL - 289
SP - 28421
EP - 28432
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 41
ER -