Document Detail

Regulation of the stability of cell surface E-cadherin by the proteasome.
MedLine Citation:
PMID:  19245796     Owner:  NLM     Status:  MEDLINE    
The epithelial-mesenchymal transition (EMT), a crucial event in cancer progression and embryonic development, is induced by transforming growth factor (TGF)-beta. Expression of E-cadherin, a representative epithelial marker, is repressed through transcriptional reduction by TGF-beta. Here, we show that endocytosis of cell surface E-cadherin during EMT induced by TGF-beta and during scattering induced by hepatocyte growth factor (HGF) can be blocked by inhibiting proteasome with lactacystin and MG132 in normal epithelial cells and in cancer cells. Although loss of cell surface E-cadherin following TGF-beta treatment induced translocation of beta-catenin, an E-cadherin-anchoring molecule, to the nucleus, proteasome inhibition prevented this process and resulted in co-localization of beta-catenin with E-cadherin at the cell surface, leading to establishment of cell-cell adhesion. However, promotion of cell migration by TGF-beta was not significantly affected by proteasome inhibition. Proteasome-dependent events thus appear to be involved in stabilization of cell surface E-cadherin.
Masao Saitoh; Takuya Shirakihara; Kohei Miyazono
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-24
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  381     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-30     Completed Date:  2009-04-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  560-5     Citation Subset:  IM    
Department of Molecular Pathology, University of Tokyo, Bunkyo-ku, Japan.
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MeSH Terms
Cadherins / genetics,  metabolism*
Cell Line
Cell Membrane / metabolism*
Epithelial Cells / cytology,  drug effects,  metabolism
Hepatocyte Growth Factor
Mesoderm / cytology,  metabolism
Proteasome Endopeptidase Complex / antagonists & inhibitors,  metabolism*
Protein Stability
Transforming Growth Factor beta / pharmacology
beta Catenin / metabolism
Reg. No./Substance:
0/Cadherins; 0/Transforming Growth Factor beta; 0/beta Catenin; 67256-21-7/Hepatocyte Growth Factor; EC Endopeptidase Complex

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