A pSMAD/CDX2 complex is essential for the intestinalization of epithelial metaplasia

Luigi Mari, Francesca Milano, Kaushal Parikh, Danielle Straub, Vincent Everts, Kees K. Hoeben, Paul Fockens, Navtej S. Buttar, Kausilia K. Krishnadath

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


The molecular mechanisms leading to epithelial metaplasias are poorly understood. Barrett's esophagus is a premalignant metaplastic change of the esophageal epithelium into columnar epithelium, occurring in patients suffering from gastroesophageal reflux disease. Mechanisms behind the development of the intestinal subtype, which is associated with the highest cancer risk, are unclear. In humans, it has been suggested that a nonspecialized columnar metaplasia precedes the development of intestinal metaplasia. Here, we propose that a complex made up of at least two factors needs to be activated simultaneously to drive the expression of intestinal type of genes. Using unique animal models and robust in vitro assays, we show that the nonspecialized columnar metaplasia is a precursor of intestinal metaplasia and that pSMAD/CDX2 interaction is essential for the switch toward an intestinal phenotype.

Original languageEnglish (US)
Pages (from-to)1197-1210
Number of pages14
JournalCell reports
Issue number4
StatePublished - May 22 2014

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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