Back to Search
Start Over
SWI/SNF chromatin-remodeling factor Smarcd3/Baf60c controls epithelial-mesenchymal transition by inducing Wnt5a signaling
- Source :
- Molecular and cellular biology. 33(15)
- Publication Year :
- 2013
-
Abstract
- We previously identified a gene signature predicted to regulate the epithelial-mesenchymal transition (EMT) in both epithelial tissue stem cells and breast cancer cells. A phenotypic RNA interference (RNAi) screen identified the genes within this 140-gene signature that promoted the conversion of mesenchymal epithelial cell adhesion molecule-negative (EpCAM-) breast cancer cells to an epithelial EpCAM+/high phenotype. The screen identified 10 of the 140 genes whose individual knockdown was sufficient to promote EpCAM and E-cadherin expression. Among these 10 genes, RNAi silencing of the SWI/SNF chromatin-remodeling factor Smarcd3/Baf60c in EpCAM- breast cancer cells gave the most robust transition from the mesenchymal to epithelial phenotype. Conversely, expression of Smarcd3/Baf60c in immortalized human mammary epithelial cells induced an EMT. The mesenchymal-like phenotype promoted by Smarcd3/Baf60c expression resulted in gene expression changes in human mammary epithelial cells similar to that of claudin-low triple-negative breast cancer cells. These mammary epithelial cells expressing Smarcd3/Baf60c had upregulated Wnt5a expression. Inhibition of Wnt5a by either RNAi knockdown or blocking antibody reversed Smarcd3/Baf60c-induced EMT. Thus, Smarcd3/Baf60c epigenetically regulates EMT by activating WNT signaling pathways.
- Subjects :
- Epithelial-Mesenchymal Transition
Chromosomal Proteins, Non-Histone
Breast Neoplasms
Biology
Wnt-5a Protein
Epigenesis, Genetic
RNA interference
Cell Line, Tumor
Proto-Oncogene Proteins
Gene silencing
Humans
Epithelial–mesenchymal transition
Breast
Molecular Biology
Wnt Signaling Pathway
Regulation of gene expression
Gene knockdown
Wnt signaling pathway
Epithelial Cells
Cell Biology
Articles
Molecular biology
SWI/SNF
Cell biology
Up-Regulation
Gene Expression Regulation, Neoplastic
Wnt Proteins
Female
RNA Interference
Stem cell
Transcription Factors
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 33
- Issue :
- 15
- Database :
- OpenAIRE
- Journal :
- Molecular and cellular biology
- Accession number :
- edsair.doi.dedup.....7d84eeccd2cea08b4921c38b929587fb