DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells.
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.
Eger
Andreas
A
Max F. Perutz Laboratories, University Department at the Vienna Biocenter, Department of Medical Biochemistry, Medical University Vienna, Vienna, Austria. andreas.eger@univie.ac.at
Aigner
Kirsten
K
Sonderegger
Stefan
S
Dampier
Brigitta
B
Oehler
Susanne
S
Schreiber
Martin
M
Berx
Geert
G
Cano
Amparo
A
Beug
Hartmut
H
Foisner
Roland
R
D001483:Base Sequence; D001943:Breast Neoplasms / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D004847:Epithelial Cells / Q000473:pathology; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D000071799:Zinc Finger E-box-Binding Homeobox 1
D015820:Cadherins; D017931:DNA Primers; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1