Oncotarget

Research Papers:

Tetraspanin-8 promotes hepatocellular carcinoma metastasis by increasing ADAM12m expression

Tingting Fang _, Jiajia Lin, Yanru Wang, Guangnan Chen, Jing Huang, Jie Chen, Yan Zhao, Ruixia Sun, Chunmin Liang and Binbin Liu

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Oncotarget. 2016; 7:40630-40643. https://doi.org/10.18632/oncotarget.9769

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Abstract

Tingting Fang1,*, Jiajia Lin1,*, Yanru Wang2, Guangnan Chen3, Jing Huang2, Jie Chen1, Yan Zhao1, Ruixia Sun1, Chunmin Liang2, Binbin Liu1

1Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, P. R. China

2Laboratory of Tumor Immunology, Department of Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, P. R. China

3The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Chunmin Liang, email: cmliang@fudan.edu.cn

Binbin Liu, email: liu.binbin@zs-hospital.sh.cn

Keywords: ADAM12, hepatocellular carcinoma, metastasis, TSPAN8

Received: October 06, 2015     Accepted: April 18, 2016     Published: June 01, 2016

ABSTRACT

Recent evidence indicates that tetraspanin-8 (TSPAN8) promotes tumor progression and metastasis. In this study, we explored the effects of TSPAN8 and the molecular mechanisms underlying hepatocellular carcinoma (HCC) metastasis using various HCC cell lines, tissues from 149 HCC patients, and animal models of HCC progression. We showed that elevated expression of TSPAN8 promoted HCC invasion in vitro and metastasis in vivo, but did not influence HCC cell proliferation in vitro. Increased TSPAN8 expression in human HCC was predictive of poor survival, and multivariate analyses indicated TSPAN8 expression to be an independent predictor for both postoperative overall survival and relapse-free survival. Importantly, TSPAN8 enhanced HCC invasion and metastasis by increasing ADAM12m expression. We therefore conclude that TSPAN8 and ADAM12m may be useful therapeutic targets for the prevention of HCC progression and metastasis.


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