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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.

Titel:	A pSMAD/CDX2 complex is essential for the intestinalization of epithelial metaplasia.
Autor/in / Beteiligte Person:	Mari, L ; Milano, F ; Parikh, K ; Straub, D ; Everts, V ; Hoeben, KK ; Fockens, P ; Buttar, NS ; Krishnadath, KK
Zeitschrift:	Cell reports, Jg. 7 (2014-05-22), Heft 4, S. 1197-210
Veröffentlichung:	[Cambridge, MA] : Cell Press, c 2012-, 2014
Medientyp:	academicJournal
ISSN:	2211-1247 (electronic)
DOI:	10.1016/j.celrep.2014.03.074
Schlagwort:	Animals Barrett Esophagus pathology Bone Morphogenetic Protein 4 biosynthesis CDX2 Transcription Factor Cell Differentiation Cell Line Disease Models, Animal Epithelium metabolism Epithelium pathology Humans Intestinal Mucosa pathology Male Metaplasia metabolism Metaplasia pathology Mice Mice, Transgenic Barrett Esophagus metabolism Homeodomain Proteins metabolism Intestinal Mucosa metabolism Smad Proteins metabolism Transcription Factors metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Cell Rep] 2014 May 22; Vol. 7 (4), pp. 1197-210. <i>Date of Electronic Publication: </i>2014 May 01. MeSH Terms: Barrett Esophagus / metabolism ; Homeodomain Proteins / metabolism ; Intestinal Mucosa / metabolism ; Smad Proteins / metabolism ; Transcription Factors / *metabolism ; Animals ; Barrett Esophagus / pathology ; Bone Morphogenetic Protein 4 / biosynthesis ; CDX2 Transcription Factor ; Cell Differentiation ; Cell Line ; Disease Models, Animal ; Epithelium / metabolism ; Epithelium / pathology ; Humans ; Intestinal Mucosa / pathology ; Male ; Metaplasia / metabolism ; Metaplasia / pathology ; Mice ; Mice, Transgenic Substance Nomenclature: 0 (BMP4 protein, human) ; 0 (Bmp4 protein, mouse) ; 0 (Bone Morphogenetic Protein 4) ; 0 (CDX2 Transcription Factor) ; 0 (CDX2 protein, human) ; 0 (Cdx2 protein, mouse) ; 0 (Homeodomain Proteins) ; 0 (Smad Proteins) ; 0 (Transcription Factors) Entry Date(s): Date Created: 20140506 Date Completed: 20150420 Latest Revision: 20161125 Update Code: 20240513

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