UMMS Affiliation

Department of Cancer Biology

Publication Date

2005-01-06

Document Type

Article

Subjects

Breast; Cadherins; 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

Disciplines

Cancer Biology | Neoplasms

Abstract

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.

DOI of Published Version

10.1083/jcb.200409067

Source

J Cell Biol. 2005 Jan 3;168(1):29-33. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of cell biology

Related Resources

Link to Article in PubMed

PubMed ID

15631989

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