DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells

Andreas Eger, Kirsten Aigner, Stefan Eugen Sonderegger, Brigitta Dampier, Susanne Oehler, Martin Schreiber, Geert Berx, Amparo Cano, Hartmut Beug, Roland Foisner

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563 Citations (Scopus)

Abstract

Downregulation of E-cadherin is a crucial event for epithelial to mesenchymal transition (EMT) in embryonic development and cancer progression. Using the EpFosER mammary tumour model we show that during EMT, upregulation of the transcription al regulator deltaEF1 coincided with transcriptional repression of E-cadherin. Ectopic expression of deltaEF1 in epithelial cells was sufficient to downregulate E-cadherin and to induce EMT. Analysis of E-cadherin promoter activity and chromatin immunoprecipitation identified deltaEF1 as direct transcriptional repressor of E-cadherin. In human cancer cells, transcript levels of deltaEF1 correlated directly with the extent of E-cadherin repression and loss of the epithelial phenotype. The protein was enriched in nuclei of human cancer cells and physically associated with the E-cadherin promoter. RNA interference-mediated downregulation of deltaEF1 in cancer cells was sufficient to derepress E-cadherin expression and restore cell to cell adhesion, suggesting that deltaEF1 is a key player in late stage carcinogenesis. A? 2005 Nature Publishing Group All rights reserved.
Original languageEnglish
Pages (from-to)2375 - 2385
Number of pages11
JournalOncogene
Volume24
Issue number14
DOIs
Publication statusPublished - 2005

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