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Proteasome inhibition causes epithelial–mesenchymal transition upon TM4SF5 expression

Authors

  • Jin Young Kim,

    1. Department of Biochemistry, School of Medicine, Cheju National University, Jeju 690-756, Korea
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  • Jae Kook Nam,

    1. Department of Biochemistry, School of Medicine, Cheju National University, Jeju 690-756, Korea
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  • Sin-Ae Lee,

    1. Cancer Research Institute, Cell Dynamics Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
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  • Mi-Sook Lee,

    1. Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
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  • Somi K. Cho,

    1. Faculty of Biotechnology, College of Applied Life Sciences, Cheju National University, Jeju 690-756, Korea
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  • Zee-Yong Park,

    1. Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea
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  • Jung Weon Lee PhD,

    Corresponding author
    1. Cancer Research Institute, Cell Dynamics Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
    2. Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
    • Department of Pharmacy, Cell Dynamics Research Center, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
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  • Moonjae Cho PhD

    Corresponding author
    1. Department of Biochemistry, School of Medicine, Cheju National University, Jeju 690-756, Korea
    • Department of Biochemistry, School of Medicine, Cheju National University, Jeju 690-756, Korea.
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Abstract

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. © 2010 Wiley-Liss, Inc.

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