肝癌是我國第二大癌癥，嚴(yán)重威脅人民健康和生命安全,，鑒定誘導(dǎo)肝癌發(fā)生和促進(jìn)肝癌發(fā)展的基因并以之為基礎(chǔ)尋找靶向藥物是近年來癌癥研究領(lǐng)域的熱點(diǎn)和重點(diǎn)之一,。
11月22日,，《肝臟病學(xué)》（Hepatology）報(bào)道了中國科學(xué)院上海生命科學(xué)研究院營養(yǎng)科學(xué)研究所謝東研究組發(fā)現(xiàn)EphrinA2促進(jìn)肝癌生長和轉(zhuǎn)移的作用及相關(guān)分子機(jī)制。該研究組博士生馮宇雄,、趙江沙等在研究中發(fā)現(xiàn),，EphrinA2基因在肝癌組織中的表達(dá)明顯高于癌旁組織；更有趣的是,，侵犯肝門靜脈的肝癌組織,，其EphrinA2基因表達(dá)增加更顯著，表明該基因的高表達(dá)很可能在肝癌的進(jìn)展中發(fā)揮重要作用,。通過對EphrinA2進(jìn)行過表達(dá)和RNA干擾兩方面的實(shí)驗(yàn)發(fā)現(xiàn),，EphrinA2能通過抑制肝癌細(xì)胞在體內(nèi)的凋亡從而提高肝癌細(xì)胞在小鼠的致瘤性及遠(yuǎn)端轉(zhuǎn)移的能力。進(jìn)一步的研究發(fā)現(xiàn),，受EphrinA2調(diào)控的蛋白激酶Akt的活化及其引發(fā)的NF-kappaB信號(hào)通路的激活在EphrinA2抑制肝癌細(xì)胞凋亡中發(fā)揮重要作用,。這些結(jié)果提示EphrinA2 通過促進(jìn)肝癌細(xì)胞存活而在肝癌的發(fā)生發(fā)展中起重要作用，EphrinA2很可能成為治療肝癌的一個(gè)潛在藥物靶點(diǎn),。
該工作得到了國家科技部,、基金委、中國科學(xué)院和上海市科委的經(jīng)費(fèi)資助,。（生物谷Bioon.com）
更多有關(guān)肝癌研究：
Cancer Research：為什么男人更易得肝癌
NEJM：microRNA表達(dá)影響肝癌復(fù)發(fā)
JAMA：原發(fā)性肝癌治療新方法
Gastroenterology：導(dǎo)致肝癌的新機(jī)制
NEJM：藥物多吉美可延長肝癌患者壽命
Hepatology：肝癌細(xì)胞轉(zhuǎn)移生物標(biāo)記
Science：引發(fā)男性高發(fā)肝癌風(fēng)險(xiǎn)的關(guān)鍵蛋白被發(fā)現(xiàn)
PLoS Pathog：寄生蟲生長激素可激發(fā)肝癌發(fā)生
J.Hepatology：患者發(fā)生肝細(xì)胞肝癌的有效預(yù)測
生物谷推薦原始出處：
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.)
