Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: implications for the epithelial-mesenchymal transition
UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
2005-01-06Keywords
BreastCadherins
Cell Line
DNA-Binding Proteins
Epithelial Cells
Female
*Gene Expression Regulation
Genes, Reporter
Glycogen Synthase Kinase 3
Humans
*Mesoderm
NF-kappa B
Phenotype
RNA, Small Interfering
Recombinant Fusion Proteins
Transcription Factors
*Transcription, Genetic
Cancer Biology
Neoplasms
Metadata
Show full item recordAbstract
We report that the activity of glycogen synthase kinase-3 (GSK-3) is necessary for the maintenance of the epithelial architecture. Pharmacological inhibition of its activity or reducing its expression using small interfering RNAs in normal breast and skin epithelial cells results in a reduction of E-cadherin expression and a more mesenchymal morphology, both of which are features associated with an epithelial-mesenchymal transition (EMT). Importantly, GSK-3 inhibition also stimulates the transcription of Snail, a repressor of E-cadherin and an inducer of the EMT. We identify NFkappaB as a transcription factor inhibited by GSK-3 in epithelial cells that is relevant for Snail expression. These findings indicate that epithelial cells must sustain activation of a specific kinase to impede a mesenchymal transition.Source
J Cell Biol. 2005 Jan 3;168(1):29-33. Link to article on publisher's siteDOI
10.1083/jcb.200409067Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26264PubMed ID
15631989Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1083/jcb.200409067