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

Oncogene. 2010 Jun 17;29(24):3490-500. doi: 10.1038/onc.2010.102. Epub 2010 Apr 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / antagonists & inhibitors*
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Dedifferentiation
  • Cell Line, Tumor
  • Colon / cytology
  • Colon / metabolism
  • Colon / pathology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • DNA Helicases / metabolism*
  • Epithelial Cells / cytology*
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / metabolism*
  • Humans
  • Mesoderm / cytology*
  • Neoplasm Invasiveness
  • Nuclear Proteins / metabolism*
  • Organ Specificity
  • Promoter Regions, Genetic / genetics
  • Protein Transport
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Zinc Finger E-box-Binding Homeobox 1


  • Cadherins
  • Homeodomain Proteins
  • Nuclear Proteins
  • Transcription Factors
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • SMARCA4 protein, human
  • DNA Helicases