E-GEOD-40145 - SWI/SNF Chromatin-Remodeling Factor Smarcd3/Baf60c Controls Epithelial-Mesenchymal Transition by Inducing Wnt5a Signaling

Status
Released on 19 August 2013, last updated on 2 June 2014
Organism
Homo sapiens
Samples (36)
Array (1)
Protocols (39)
Description
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. sampleXreference
Experiment type
transcription profiling by array 
Contacts
Charles Perou <cperou@med.unc.edu>, Aleix Prat, Charles M Perou, Gary L Johnson, Nicole V Jordan
Citation
SWI/SNF Chromatin-Remodeling Factor Smarcd3/Baf60c Controls Epithelial-Mesenchymal Transition by Inducing Wnt5a Signaling. Jordan NV, Prat A, Abell AN, Zawistowski JS, Sciaky N, Karginova OA, Zhou B, Golitz BT, Perou CM, Johnson GL. , Europe PMC 23716599
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-40145.idf.txt
Sample and data relationshipE-GEOD-40145.sdrf.txt
Processed data (1)E-GEOD-40145.processed.1.zip
Array designA-GEOD-7504.adf.txt
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