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01-09-2008 | Research Paper

TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression

Authors: Zhuan Zhou, Yu-Liang Ran, Hai Hu, Jian Pan, Zhi-Feng Li, Li-Zhao Chen, Li-Chao Sun, Liang Peng, Xi-Lu Zhao, Long Yu, Li-Xin Sun, Zhi-Hua Yang

Published in: Clinical & Experimental Metastasis | Issue 5/2008

Abstract

Esophageal cancer is characterized by rapid clinical progression and poor prognosis due to adjacent tissue invasion and distant organs metastasis at a very early stage. TM4SF3 (transmembrane 4 superfamily 3), a member of tetraspanin family, has been reported as a metastasis associated gene in many types of tumors. Herein, we described new properties of TM4SF3 in tumor metastasis, which suggested that this gene might be involved in esophageal carcinoma metastasis. Western blotting revealed that TM4SF3 was overexpressed in 57.1% (8/14) of esophageal carcinomas and esophageal carcinoma cell lines with high-invasive potential. Exogenous expression of TM4SF3 in two low-invasive esophageal carcinoma cell lines, KYSE150 and EC9706, significantly promoted cell migration and invasion. Upregulating TM4SF3 expression in EC9706 cells promoted xenograft tumor invading into surrounding tissues, enhanced lung metastasis, and shortened the lifespan of mice (median survival EC9706-TM4SF3 106.5 days versus EC9706-Vector 169.0 days, P < 0.0001) in a spontaneous metastasis model. Further studies demonstrated that ADAM12m was upregulated by TM4SF3 overexpression in vitro and in vivo. Abrogating up-expression of ADAM12m by siRNA significantly suppressed TM4SF3-mediated invasion. Together, these data from our studies indicated that overexpression of TM4SF3 in esophageal cancer conferred advantage to the invasion and metastasis of this destructive disease. Upregulated expression of ADAM12m by TM4SF3 might play a key role in TM4SF3-mediated invasion and metastasis. TM4SF3 and ADAM12m might be potential targets of esophageal carcinoma for anti-metastasis therapy.

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Title: TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression
Authors: Zhuan Zhou
Yu-Liang Ran
Hai Hu
Jian Pan
Zhi-Feng Li
Li-Zhao Chen
Li-Chao Sun
Liang Peng
Xi-Lu Zhao
Long Yu
Li-Xin Sun
Zhi-Hua Yang
Publication date: 01-09-2008
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 5/2008
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-008-9168-0

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