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

被引：104

作者：

Lee, Sin-Ae ^{[1
,2
]}

Lee, Sung-Yul ^{[1
,2
]}

Cho, Ik-Hyun ^{[3
,4
]}

Oh, Min-A ^{[1
,2
,5
]}

Kang, Eun-Sil ^{[1
,2
]}

Kim, Yong-Bae ^{[1
,2
,5
]}

Seo, Woo Duck ^{[6
]}

Choi, Suyong ^{[1
,2
,5
]}

Nam, Ju-Ock ^{[7
]}

Tamamori-Adachi, Mimi ^{[8
]}

Kitajima, Shigetaka ^{[8
]}

Ye, Sang-Kyu ^{[9
]}

Kim, Semi ^{[10
]}

Hwang, Yoon-Jin ^{[11
]}

Kim, In-San ^{[7
]}

Park, Ki Hun ^{[6
]}

Lee, Jung Weon ^{[1
,2
,5
]}

机构：

[1] Seoul Natl Univ, Coll Med, Dept Mol & Clin Oncol, Canc Res Inst, Seoul 110799, South Korea

[2] Seoul Natl Univ, Cell Dynam Res Ctr, Seoul 110799, South Korea

[3] Seoul Natl Univ, Coll Dent, Seoul 110799, South Korea

[4] Seoul Natl Univ, Dent Res Inst, Seoul 110799, South Korea

[5] Seoul Natl Univ, Dept Tumor Biol, Seoul 110799, South Korea

[6] Gyeongsang Natl Univ, Div Appl Life Sci, Jinju, South Korea

[7] Kyungpook Natl Univ, Sch Med, Dept Biochem, Taegu, South Korea

[8] Tokyo Med & Dent Univ, Dept Biochem Genet, Tokyo, Japan

[9] Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul 110799, South Korea

[10] Korea Res Inst Biosci & Biotechnol, Taejon, South Korea

[11] Kyungpook Natl Univ, Sch Med, Dept Surg, Taegu, South Korea

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2008年 / 118卷 / 04期

关键词：

D O I：

10.1172/JCI33768

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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 p27(KiP1) 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 p27(KiP1), 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.

引用

页码：1354 / 1366

页数：13

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