Source:http://linkedlifedata.com/resource/pubmed/id/20418909
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
24
|
| pubmed:dateCreated |
2010-6-17
|
| pubmed:abstractText |
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.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SMARCA4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/ZEB1 protein, human
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
1476-5594
|
| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:day |
17
|
| pubmed:volume |
29
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3490-500
|
| pubmed:meshHeading |
pubmed-meshheading:20418909-Cadherins,
pubmed-meshheading:20418909-Cell Dedifferentiation,
pubmed-meshheading:20418909-Cell Line, Tumor,
pubmed-meshheading:20418909-Colon,
pubmed-meshheading:20418909-Colonic Neoplasms,
pubmed-meshheading:20418909-DNA Helicases,
pubmed-meshheading:20418909-Epithelial Cells,
pubmed-meshheading:20418909-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:20418909-Homeodomain Proteins,
pubmed-meshheading:20418909-Humans,
pubmed-meshheading:20418909-Mesoderm,
pubmed-meshheading:20418909-Neoplasm Invasiveness,
pubmed-meshheading:20418909-Nuclear Proteins,
pubmed-meshheading:20418909-Organ Specificity,
pubmed-meshheading:20418909-Promoter Regions, Genetic,
pubmed-meshheading:20418909-Protein Transport,
pubmed-meshheading:20418909-Transcription, Genetic,
pubmed-meshheading:20418909-Transcription Factors
|
| pubmed:year |
2010
|
| pubmed:articleTitle |
ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1.
|
| pubmed:affiliation |
Group of Transcriptional Regulation, Department of Oncology and Hematology, IDIBAPS, Barcelona, Spain.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|