EphA2 promotes epithelial-mesenchymal transition through the Wnt/β-catenin pathway in gastric cancer cells

被引：209

作者：

Huang, J. ^{[1
]}

Xiao, D. ^{[2
]}

Li, G. ^{[3
]}

Ma, J. ^{[3
]}

Chen, P. ^{[3
]}

Yuan, W. ^{[4
]}

Hou, F. ^{[4
]}

Ge, J. ^{[4
]}

Zhong, M. ^{[1
]}

Tang, Y. ^{[1
]}

Xia, X. ^{[5
]}

Chen, Z. ^{[4
]}

机构：

[1] Cent S Univ, Xiangya Hosp, Dept Oncol, Changsha 410008, Hunan, Peoples R China

[2] Cent S Univ, Xiangya Hosp, Dept Pathol, Changsha 410008, Hunan, Peoples R China

[3] Cent S Univ, Hunan Key Lab Nonresolving Inflammat & Canc, Canc Res Inst, Changsha 410008, Hunan, Peoples R China

[4] Cent S Univ, Xiangya Hosp, Dept Gen Surg, Changsha 410008, Hunan, Peoples R China

[5] Weill Cornell Sch Med, Methodist Hosp Res Inst, Ctr Genom Med, Houston, TX USA

来源：

ONCOGENE | 2014年 / 33卷 / 21期

关键词：

EphA2; gastric cancer; epithelial-mensenchymal transition; Wnt/beta-catenin; DEPENDENT TRANSCRIPTION; COLORECTAL-CANCER; RECEPTOR; ACTIVATION; EXPRESSION;

D O I：

10.1038/onc.2013.238

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

This study aims to investigate the significance of erythropoietin-producing hepatocellular (Eph)A2 expression and the mechanism by which EphA2 is involved in the epithelial-mensenchymal transition (EMT) of gastric cancer cells. EphA2 expression levels were upregulated and positively correlated with metastasis and EMT markers in human gastric cancer specimens. Modulation of EphA2 expression levels had distinct effects on cell proliferation, cell cycle, migration, invasion and morphology in the gastric cancer cell lines SGC7901 and AGS in vitro and in vivo. Overexpression of EphA2 resulted in the upregulation of the EMT molecular markers N-cadherin and Snail, as well as the Wnt/beta-catenin targets TCF4, Cyclin-D1 and c-Myc, while silencing EphA2 using short hairpin RNA had the opposite effect. Furthermore, inhibition of the Wnt/beta-catenin pathway by XAV939 negated the effect of EphA2 overexpression, whereas activation of the Wnt/beta-catenin pathway by LiCl impaired the effect of the EphA2 knockdown on EMT. These observations demonstrate that EphA2 upregulation is a common event in gastric cancer specimens that is closely correlated with cancer metastasis and that EphA2 promotes EMT of gastric cancer cells through activation of Wnt/beta-catenin signaling.

引用

页码：2737 / 2747

页数：11

共 31 条

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