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

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 transcriptional 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.

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Acknowledgements

We thank Bernd Schüttengruber and Christian Seiser, Medical University Vienna, for their technical advice regarding the ChIP analyses, Josef Gotzmann, Medical University Vienna, for help with RNAi experiments and Gabriele Stengl and Peter Steinlein, Institute of Molecular Pathology, Vienna, for Flow Cytometry (FACS) experiments. In addition, we thank Wolfgang Mikulits, Cancer Research Institute Vienna, for his critical comments on the manuscript. This study was supported by grants from the Austrian Science Research Fund (FWF) No. SFB 006 to RF (603) and HB (612), by funds from the ‘Hochschuljubiläumsstifting’ of the city of Vienna to AE, and by funds of the Austrian Ministry of Education, Science, and the Arts (Austrian Genome Research Program GEN-AU) to MS.

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Correspondence to Andreas Eger or Roland Foisner.

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Eger, A., Aigner, K., Sonderegger, S. et al. DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene 24, 2375–2385 (2005). https://doi.org/10.1038/sj.onc.1208429

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