Regulation of the stability of cell surface E-cadherin by the proteasome.
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.
Saitoh
Masao
M
Department of Molecular Pathology, University of Tokyo, Bunkyo-ku, Japan. msaitoh-ind@umin.ac.jp
Shirakihara
Takuya
T
Miyazono
Kohei
K
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D004705:Endocytosis; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017228:Hepatocyte Growth Factor; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D055550:Protein Stability; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; D061988:Proteasome Inhibitors; D016212:Transforming Growth Factor beta; D051176:beta Catenin; D017228:Hepatocyte Growth Factor; D046988:Proteasome Endopeptidase Complex