肝癌是我国第二大癌症，严重威胁人民健康和生命安全，鉴定诱导肝癌发生和促进肝癌发展的基因并以之为基础寻找靶向药物是近年来癌症研究领域的热点和重点之一。
11月22日，《肝脏病学》（Hepatology）报道了中国科学院上海生命科学研究院营养科学研究所谢东研究组发现EphrinA2促进肝癌生长和转移的作用及相关分子机制。该研究组博士生冯宇雄、赵江沙等在研究中发现，EphrinA2基因在肝癌组织中的表达明显高于癌旁组织；更有趣的是，侵犯肝门静脉的肝癌组织，其EphrinA2基因表达增加更显著，表明该基因的高表达很可能在肝癌的进展中发挥重要作用。通过对EphrinA2进行过表达和RNA干扰两方面的实验发现，EphrinA2能通过抑制肝癌细胞在体内的凋亡从而提高肝癌细胞在小鼠的致瘤性及远端转移的能力。进一步的研究发现，受EphrinA2调控的蛋白激酶Akt的活化及其引发的NF-kappaB信号通路的激活在EphrinA2抑制肝癌细胞凋亡中发挥重要作用。这些结果提示EphrinA2 通过促进肝癌细胞存活而在肝癌的发生发展中起重要作用，EphrinA2很可能成为治疗肝癌的一个潜在药物靶点。
该工作得到了国家科技部、基金委、中国科学院和上海市科委的经费资助。（生物谷Bioon.com）
更多有关肝癌研究：
Cancer Research：为什么男人更易得肝癌
NEJM：microRNA表达影响肝癌复发
JAMA：原发性肝癌治疗新方法
Gastroenterology：导致肝癌的新机制
NEJM：药物多吉美可延长肝癌患者寿命
Hepatology：肝癌细胞转移生物标记
Science：引发男性高发肝癌风险的关键蛋白被发现
PLoS Pathog：寄生虫生长激素可激发肝癌发生
J.Hepatology：患者发生肝细胞肝癌的有效预测
生物谷推荐原始出处：
Hepatology 14 Sep 2009 DOI:10.1002/hep.23313
Liver cancer: EphrinA2 promotes tumorigenicity through Rac1/Ak/NF-kB signaling pathway
Yu-Xiong Feng 1 5, Jiang-Sha Zhao 1 5, Jing-Jing Li 1, Tao Wang 2, Shu-Qun Cheng 2, Yunfei Yuan 3, Fudi Wang 1, Xiao-Fan Wang 4, Dong Xie 1 6 *§
1Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
2The Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China
3State Key Laboratory of Oncology in South China and Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
4Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC
5Graduate School of Chinese Academy of Sciences, Shanghai, China
6Key laboratory of Nutrition and Metabolism, Chinese Academy of Sciences, Shanghai, China
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-)-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-B) 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.)
