ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1.

Loss of E-cadherin is a key initial step in the transdifferentiation of epithelial cells to a mesenchymal phenotype, which occurs when tumor epithelial cells invade into surrounding tissues. Expression of the nuclear factor ZEB1 induces an epithelial-to-mesenchymal transition and confers a metastatic phenotype on carcinomas by repressing the E-cadherin gene ...
at the transcriptional level. In this study, we show that ZEB1 interacts with the SWI/SNF chromatin-remodeling protein BRG1 to regulate E-cadherin independently of CtBP, its traditional co-repressor. Blocking the interaction between ZEB1 and BRG1 induces expression of E-cadherin and downregulation of the mesenchymal marker vimentin. ZEB1 and BRG1 colocalize in E-cadherin-negative cells from cancer lines and in the stroma of normal colon. Colocalization of ZEB1 and BRG1 in epithelial cells is only found in those de-differentiated cells characterized by nuclear beta-catenin staining at the invasive edge of the tumor. Our results identify ZEB1/BRG1 as a new transcriptional mechanism regulating E-cadherin expression and epithelial-to-mesenchymal transdifferentiation that may be involved during the initial stages of tumor invasion.
Mesh Terms:
Cadherins, Cell Dedifferentiation, Cell Line, Tumor, Colon, Colonic Neoplasms, DNA Helicases, Epithelial Cells, Gene Expression Regulation, Neoplastic, Homeodomain Proteins, Humans, Mesoderm, Neoplasm Invasiveness, Nuclear Proteins, Organ Specificity, Promoter Regions, Genetic, Protein Transport, Transcription Factors, Transcription, Genetic
Oncogene
Date: Jun. 17, 2010
Download Curated Data For This Publication
117469
Switch View:
  • Interactions 2