Abstract 4109: EphrinA2 promotes tumorigenicity through Rac1/Akt/NF-kappa B signaling pathway in liver cancer

Eph/Ephrin family, one of the largest receptor tyrosine kinase families, has been extensively studied in morphogenesis and neural development. Recently, growing attentions have been attracted on its role in 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 upregulated in both established cell lines and clinical tissue samples of HCC, and the most significant increase was observed in the tumors invading into the portal veins. Forced expression of EphrinA2 in HCC cells significantly promoted in vivo tumorigenicity, while 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 TNF-alpha-induced apoptosis, thus facilitating their survival. Furthermore, we disclosed a novel EphrinA2/Rac1/Akt/NF-kB pathway contributing to the inhibitory effect on apoptosis in HCC cells. In a conclusion, our 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 Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4109.