Tetraspanin TM4SF5 mediates loss of contact inhibition through epithelial-mesenchymal transition in human hepatocarcinoma

Sin Ae Lee, Sung Yul Lee, Ik Hyun Cho, Min A. Oh, Eun Sil Kang, Yong Bae Kim, Duck Seo Woo, Suyong Choi, Ju Ock Nam, Mimi Tamamori-Adachi, Shigetaka Kitajima, Sang Kyu Ye, Semi Kim, Yoon Jin Hwang, In San Kim, Hun Park Ki, Weon Lee Jung

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

The growth of normal cells is arrested when they come in contact with each other, a process known as contact inhibition. Contact inhibition is lost during tumorigenesis, resulting in uncontrolled cell growth. Here, we investigated the role of the tetraspanin transmembrane 4 superfamily member 5 (TM4SF5) in contact inhibition and tumorigenesis. We found that TM4SF5 was overexpressed in human hepatocarcinoma tissue. TM4SF5 expression in clinical samples and in human hepatocellular carcinoma cell lines correlated with enhanced p27Kip1 expression and cytosolic stabilization as well as morphological elongation mediated by RhoA inactivation. These TM4SF5-mediated effects resulted in epithelial-mesenchymal transition (EMT) via loss of E-cadherin expression. The consequence of this was aberrant cell growth, as assessed by S-phase transition in confluent conditions, anchorage-independent growth, and tumor formation in nude mice. The TM4SF5-mediated effects were abolished by suppressing the expression of either TM4SF5 or cytosolic p27Kip1, as well as by reconstituting the expression of E-cadherin. Our observations have revealed a role for TM4SF5 in causing uncontrolled growth of human hepatocarcinoma cells through EMT.

Original languageEnglish
Pages (from-to)1354-1366
Number of pages13
JournalJournal of Clinical Investigation
Volume118
Issue number4
DOIs
Publication statusPublished - 2008 Apr 1

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Tetraspanin TM4SF5 mediates loss of contact inhibition through epithelial-mesenchymal transition in human hepatocarcinoma'. Together they form a unique fingerprint.

  • Cite this

    Lee, S. A., Lee, S. Y., Cho, I. H., Oh, M. A., Kang, E. S., Kim, Y. B., Woo, D. S., Choi, S., Nam, J. O., Tamamori-Adachi, M., Kitajima, S., Ye, S. K., Kim, S., Hwang, Y. J., Kim, I. S., Ki, H. P., & Jung, W. L. (2008). Tetraspanin TM4SF5 mediates loss of contact inhibition through epithelial-mesenchymal transition in human hepatocarcinoma. Journal of Clinical Investigation, 118(4), 1354-1366. https://doi.org/10.1172/JCI33768