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

Cited 81 time in Web of Science Cited 83 time in Scopus
Authors
Lee, Sin-Ae; Lee, Sung-Yul; Cho, Ik-Hyun; Oh, Min-A; Kang, Eun-Sil; Kim, Yong-Bae; Seo, Woo Duck; Choi, Suyong; Nam, Ju-Ock; Tamamori-Adachi, Mimi; Kitajima, Shigetaka; Ye, Sang-Kyu; Kim, Semi; Hwang, Yoon-Jin; Kim, In-San; Park, Ki Hun; Lee, Jung Weon
Issue Date
2008-03-22
Publisher
American Society for Clinical Investigation
Citation
J Clin Invest. 118(4):1354-1366
Keywords
AnimalsCarcinoma, Hepatocellular/genetics/metabolism/*pathologyCell CommunicationCell Line*Contact InhibitionCyclin-Dependent Kinase Inhibitor p27/genetics/metabolismCytosol/metabolismEnzyme ActivationEpithelial Cells/*metabolism/*pathologyGene Expression RegulationHumansMembrane Proteins/genetics/*metabolismMesoderm/*metabolism/*pathologyMiceNeoplasm TransplantationrhoA GTP-Binding Protein/metabolism
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.
ISSN
0021-9738 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18357344

http://hdl.handle.net/10371/67674
DOI
https://doi.org/10.1172/JCI33768
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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