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

Oncogene volume 33, pages 2737–2747 (2014)Cite this article

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Abstract

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/β-catenin targets TCF4, Cyclin-D1 and c-Myc, while silencing EphA2 using short hairpin RNA had the opposite effect. Furthermore, inhibition of the Wnt/β-catenin pathway by XAV939 negated the effect of EphA2 overexpression, whereas activation of the Wnt/β-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/β-catenin signaling.

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Acknowledgements

This work was supported by Nature Scientific Foundation of China (81172297), Ministry of Education (NCET-11-0520, SRF for ROCS) and Hunan Province Natural Sciences Foundation of China (B2010-010). We thank Yangchun Xie and Liyang Zhang for their technical help.

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Authors and Affiliations

  1. Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China

    J Huang, M Zhong & Y Tang

  2. Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China

    D Xiao

  3. Cancer Research Institute, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Central South University, Changsha, Hunan, China

    G Li, J Ma & P Chen

  4. Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China

    W Yuan, F Hou, J Ge & Z Chen

  5. Center for Genomic Medicine, The Methodist Hospital Research Institute, Weill Cornell School of Medicine, Houston, TX, USA

    X Xia

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Correspondence to Z Chen.

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Huang, J., Xiao, D., Li, G. et al. EphA2 promotes epithelial–mesenchymal transition through the Wnt/β-catenin pathway in gastric cancer cells. Oncogene 33, 2737–2747 (2014). https://doi.org/10.1038/onc.2013.238

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