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

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

in Apoptosis / Base Sequence / Biochemistry / Breast cancer / Breast Neoplasms - pathology / Cadherins - genetics / Cadherins - metabolism / Cancer / Carcinogenesis / Cell adhesion / Cell adhesion & migration / Cell Biology / Chromatin / DNA Primers / E-cadherin / Ectopic expression / Embryogenesis / Epithelial cells / Epithelial Cells - pathology / Gene silencing / Homeodomain Proteins - physiology / Human Genetics / Humans / Immunoprecipitation / Internal Medicine / Kinases / Medicine / Medicine & Public Health / Mesenchyme / Metastasis / Mutation / Oncology / original-paper / Phenotypes / Promoter Regions, Genetic / Proteins / Repressor Proteins - physiology / RNA-mediated interference / Transcription Factors - physiology / Transcription, Genetic - physiology / Tumors / Zinc Finger E-box-Binding Homeobox 1

2005

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

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

2005

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

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

2005

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Journal Article

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

Aigner, Kirsten,

Oehler, Susanne,

Beug, Hartmut,

Cano, Amparo,

Berx, Geert,

Foisner, Roland,

Eger, Andreas,

Sonderegger, Stefan,

Schreiber, Martin,

Dampier, Brigitta

2005

Overview

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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Publisher

Nature Publishing Group UK,Nature Publishing Group

Subject

/ Breast Neoplasms - pathology

/ Cadherins - genetics

/ Cadherins - metabolism