Tetraspanin TM4SF5 Mediates Loss of Contact Inhibition Through Epithelial-mesenchymal Transition in Human Hepatocarcinoma

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2008 Mar 22

PMID 18357344

Citations 54

Authors

Sin-Ae Lee

Sung-Yul Lee

Ik-Hyun Cho

Min-A Oh

Eun-Sil Kang

Yong-Bae Kim

Woo Duck Seo

Suyong Choi

Ju-Ock Nam

Mimi Tamamori-Adachi

Shigetaka Kitajima

Sang-Kyu Ye

Semi Kim

Yoon-Jin Hwang

In-San Kim

Ki Hun Park

Jung Weon Lee

Affiliations

Soon will be listed here.

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.

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