Liver cancer: EphrinA2 promotes tumorigenicity through Rac1/Akt/NF-κB signaling pathway

Authors

  • Yu-Xiong Feng,

    1. Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    2. Graduate School of Chinese Academy of Sciences, Shanghai, China
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    • These authors contributed equally to this study.

  • Jiang-Sha Zhao,

    1. Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    2. Graduate School of Chinese Academy of Sciences, Shanghai, China
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  • Jing-Jing Li,

    1. Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Tao Wang,

    1. The Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China
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  • Shu-Qun Cheng,

    1. The Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China
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  • Yunfei Yuan,

    1. State Key Laboratory of Oncology in South China and Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
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  • Fudi Wang,

    1. Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Xiao-Fan Wang,

    1. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC
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  • Dong Xie

    Corresponding author
    1. Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    2. Key laboratory of Nutrition and Metabolism, Chinese Academy of Sciences, Shanghai, China
    • Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Tai-Yuan Rd. Shanghai 200031, China===

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    • fax: (86)-21-54920291


  • Potential conflict of interest: Nothing to report.

  • This is a corrected version of the title first published on 16 November 2009 — the corrected version appears in print. In the originally published version, “akt” was misspelled as “ak”.

Abstract

Eph/Ephrin family, one of the largest receptor tyrosine kinase families, has been extensively studied in morphogenesis and neural development. Recently, growing attention has been paid to its role in the initiation and progression of various cancers. However, the role of Eph/Ephrins in hepatocellular carcinoma (HCC) has been rarely investigated. In this study, we found that the expression of EphrinA2 was significantly up-regulated in both established cell lines and clinical tissue samples of HCC, and the most significant increase was observed in the tumors invading the portal veins. Forced expression of EphrinA2 in HCC cells significantly promoted in vivo tumorigenicity, whereas knockdown of this gene inhibited this oncogenic effect. We further found that suppression of apoptosis, rather than accelerating proliferation, was responsible for EphrinA2-enhanced tumorigenicity. In addition, EphrinA2 endowed cancer cells with resistance to tumor necrosis factor alpha (TNF-α)–induced apoptosis, thus facilitating their survival. Furthermore, we disclosed a novel EphrinA2/ras-related c3 botulinum toxin substrate 1 (Rac1)/V-akt murine thymoma viral oncogene homolog (Akt)/nuclear factor-kappa B (NF-κB) pathway contributing to the inhibitory effect on apoptosis in HCC cells. Conclusion: This study revealed that EphrinA2 played an important role in the development and progression of HCC by promoting the survival of cancer cells, indicating its role as a potential therapeutic target in HCC. (HEPATOLOGY 2010.)

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