腺病毒介导的EMC6基因通过下调FAK信号通路抑制胃癌细胞迁移  

The Adenovirus Vector-mediated Expression of EMC6 Inhibits Migration of Gastric Cancer Cells via Down-regulating the FAK Signaling Pathway

作　　者：夏艳[1,2] 李日勇 王晓琨[2] 洪杜北琪 林欣[1,2] 于佳弘 陈英玉[1,2] XIA Yan1,2, LI Ri-Yong1,2, WANG Xiao-Kun2, HONGDU Bei-Qi1,2, LIN Xin1,2, YU Jia-Hong1,2, CHEN Ying-Yu1,2(1. Department of Immunology, School of Basic Medical Science, Peking University, Beijing 100191, China ; 2.Peking University Center for Human Disease Genomics , Beijing 100191, Chin)

机构地区：[1]北京大学基础医学院免疫学系,北京100191 [2]北京大学人类疾病基因研究中心,北京100191

出　　处：《中国生物化学与分子生物学报》2018年第3期285-292,共8页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No.81420108002;No.31370898)资助~~

摘　　要：内质网膜蛋白复合物亚单位6(endoplasmic reticulum membrane protein complex subunit 6,EMC6),也称穿膜蛋白93(transmembrane protein 93,TMEM93)是我们首次报道的一个人类自噬相关分子。EMC6基因进化保守,表达广泛,在胃癌组织中表达下调或缺失。本研究利用构建的重组腺病毒5型EMC6(Ad5-EMC6)载体,感染胃癌细胞系BGC823和SGC7901,分析了其在肿瘤细胞的表达以及抗肿瘤活性。研究证明,Ad5-EMC6能够显著抑制胃癌细胞的克隆形成、细胞划痕修复、以及迁移和侵袭的能力。进一步的研究提示,Ad5-EMC6能够降低胃癌细胞局部黏着斑激酶(FAK)的Y576/577磷酸化水平,FAK下游的基质金属蛋白酶MMP2和MMP9的蛋白质水平也同时下调。在裸鼠的腹膜扩散模型中,Ad5-EMC6处理组的小鼠腹膜结节数量明显减少或缺失。这些研究数据提示,Ad5-EMC6介导的FAK信号灭活可能是其抑瘤活性的机制之一,其分子机制还需要进一步探讨。Endoplasmic reticulum membrane protein complex subunit 6（ EMC6）,also known as transmembrane protein 93（ TMEM93）,is a novel human autophagy-related molecule identified in our laboratory. The EMC6 gene is conserved and expressed widely in a variety of tissues and organs.However,under abnormal conditions the expression of EMC6 was reduced or absent e. g. in gastric cancer tissues. In this report,we constructed a recombinant adenovirus 5-EMC6（ Ad5-EMC6） vector and evaluated its expression and anti-tumor activities in BGC823 and SGC7901 gastric cancer cells.Colony formation analysis revealed that the adenovirus increased the production of EMC6 protein and inhibited tumor cell growth. The ability of migration and invasion was also reduced in cells infected by Ad5-EMC6. Further studies suggested that Ad5-EMC6 could decrease the phosphorylation levels of FAK at Y576/577,as well as the levels of MMP2 and MMP9 proteins. Data obtained from an animal model ofperitoneal metastasis proved that the number of metastatic nodules in the peritoneal cavity was significantly decreased or absent in the Ad5-EMC6 group compared with the Ad5-Null group.Collectively,these data suggested that Ad5-EMC6 mediated the inhibition of the FAK signaling pathway,and it may be one of the mechanisms of its anti-tumor activity.

关 键 词：内质网膜蛋白复合物亚单位6(EMC6) 胃癌 迁移 侵袭 局部黏着斑激酶 

分 类 号：Q25[生物学—细胞生物学] Q731