Transcriptional regulation of the intestinal nuclear bile acid Farnesoid X Receptor (FXR) by the caudal-related homeobox 2 (CDX2)

Salvatore Modica, Marica Cariello, Annalisa Morgano, Isabelle Gross, Maria Carmela Vegliante, Stefania Murzilli, Lorena Salvatore, Jean Noel Freund, Carlo Sabbà, Antonio Moschetta

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)28421-28432
Number of pages12
JournalJournal of Biological Chemistry
Volume289
Issue number41
DOIs
Publication statusPublished - Oct 10 2014

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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