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

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34 Scopus citations

Abstract

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
Volume7
Issue number4
DOIs
StatePublished - May 22 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mari, L., Milano, F., Parikh, K., Straub, D., Everts, V., Hoeben, K. K., Fockens, P., Buttar, N. S., & Krishnadath, K. K. (2014). A pSMAD/CDX2 complex is essential for the intestinalization of epithelial metaplasia. Cell reports, 7(4), 1197-1210. https://doi.org/10.1016/j.celrep.2014.03.074