Proteasome inhibition causes epithelial-mesenchymal transition upon TM4SF5 expression.
- Kim, Jin Young; Nam, Jae Kook; Lee, Sin-Ae; Lee, Mi-Sook; Cho, Somi K.; Park, Zee-Yong; Lee, Jung Weon; Cho, Moonjae
- Issue Date
- JOURNAL OF CELLULAR BIOCHEMISTRY Vol.112 No.3, pp. 782-792
- 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.
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