Proteasome Inhibition Causes Epithelial-Mesenchymal Transition upon TM4SF5 Expression

作者：Kim Jin Young; Nam Jae Kook; Lee Sin Ae; Lee Mi Sook; Cho Somi K; Park Zee Yong; Lee Jung Weon^*; Cho Moonjae

来源：Journal of Cellular Biochemistry, 2011, 112(3): 782-792.

DOI：10.1002/jcb.22954

• EPITHELIAL-MESENCHYMAL TRANSITION/PROTEASOME/TETRASPAN/TRANSCRIPTION

Transmembrane 4 L six family member 5 (TM4SF5) is highly expressed in hepatocarcinoma and causes epithelial-mesenchymal transition (EMT) of hepatocytes. We found that TM4SF5-expressing cells showed lower mRNA levels but maintained normal protein levels in certain gene cases, indicating that TM4SF5 mediates stabilization of proteins. In this study, we explored whether regulation of proteasome activity and TM4SF5 expression led to EMT. We observed that TM4SF5 expression caused inhibition of proteasome activity and proteasome subunit expression, causing morphological changes and loss of cell-cell contacts. shRNA against TM4SF5 recovered proteasome expression, with leading to blockade of proteasome inactivation and EMT. Altogether, TM4SF5 expression appeared to cause loss of cell-cell adhesions via proteasome suppression and thereby proteasome inhibition, leading to repression of cell-cell adhesion molecules, such as E-cadherin. J. Cell. Biochem. 112: 782-792, 2011.

• 出版日期2011-3