SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions

Cindy Vandewalle, Joke Comijn, Bram De Craene, Petra Vermassen, Erik Bruyneel, Henriette Andersen, Eugene Tulchinsky, Frans Van Roy, Geert Berx

Research output: Contribution to journalArticlepeer-review

382 Citations (Scopus)

Abstract

SIP1/ZEB2 is a member of the δEF-1 family of two-handed zinc finger nuclear factors. The expression of these transcription factors is associated with epithelial mesenchymal transitions (EMT) during development. SIP1 is also expressed in some breast cancer cell lines and was detected in intestinal gastric carcinomas, where its expression is inversely correlated with that of E-cadherin. Here, we show that expression of SIP1 in human epithelial cells results in a clear morphological change from an epithelial to a mesenchymal phenotype. Induction of this epithelial dedifferentiation was accompanied by repression of several cell junctional proteins, with concomitant repression of their mRNA levels. Besides E-cadherin, other genes coding for crucial proteins of tight junctions, desmosomes and gap junctions were found to be transcriptionally regulated by the transcriptional repressor SIP1. Moreover, study of the promoter regions of selected genes by luciferase reporter assays and chromatin immunoprecipitation shows that repression is directly mediated by SIP1. These data indicate that, during epithelial dedifferentiation, SIP1 represses in a coordinated manner the transcription of genes coding for junctional proteins contributing to the dedifferentiated state; this repression occurs by a general mechanism mediated by Smad Interacting Protein 1 (SIP1)-binding sites.

Original languageEnglish
Pages (from-to)6566-6578
Number of pages13
JournalNucleic Acids Research
Volume33
Issue number20
DOIs
Publication statusPublished - Dec 27 2005
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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