Ad5-EMC6 mediates antitumor activity in gastric cancer cells through the mitochondrial apoptosis pathway
Ad5-EMC6 mediates antitumor activity in gastric cancer cells through the mitochondrial apoptosis pathway
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Ad5-EMC6通过线粒体凋亡途径介导胃癌细胞的抗肿瘤活性
DOI：
10.1016/j.bbrc.2019.04.023
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发表时间：
2019-06-04
影响因子：
3.1
通讯作者：
Chen, Yingyu
中科院分区：
文献类型：
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作者：
Li, Riyong;Wang, Xiaokun;Chen, Yingyu
内质网膜蛋白复合物亚基6（EMC6），又称跨膜蛋白93（transmembrane Protein 93，TMEM93），是一种自噬相关蛋白。 EMC6 过度表达可抑制癌细胞生长并诱导细胞凋亡，但 EMC6 的相互作用伙伴及其细胞作用仍不完全清楚。在本研究中，我们报道了腺病毒介导的BGC823和SGC7901胃癌细胞中EMC6（Ad5-EMC6）的异位过表达降低了ERK1/2的活性，下调了BCL-2蛋白和磷酸化BCL-2的水平，增加了tBID和BAX的表达，并降低了线粒体膜电位，随后导致细胞凋亡。在异种移植肿瘤模型中，我们发现Ad5-EMC6会损害裸鼠SGC7901胃癌细胞的肿瘤发生。此外，Ad5-EMC6 还能增强胃癌细胞对化疗药物依托泊苷的敏感性。总的来说，这些结果表明 EMC6 诱导的胃癌细胞凋亡至少部分通过线粒体介导的凋亡途径发生。我们的研究为 Ad5-EMC6 在胃癌中的潜在临床应用提供了合理的基础。 (C) 2019 Elsevier Inc. 保留所有权利。
Endoplasmic reticulum membrane protein complex subunit 6 (EMC6), also known as transmembrane protein 93 (transmembrane protein 93, TMEM93), is an autophagy-related protein. EMC6 overexpression inhibits cancer cell growth and induces apoptosis, but the interaction partners of EMC6 and its cellular responsibilities remain incompletely understood. In this study, we report that adenovirus-mediated ectopic overexpression of EMC6 (Ad5-EMC6) in BGC823 and SGC7901 gastric cancer cells decreases the activity of ERK1/2, down-regulates the levels of BCL-2 protein and phosphorylated BCL-2, increases the expression of tBID and BAX, and decreases mitochondrial membrane potential and subsequently leading to cell apoptosis. In a xenograft tumor model, we found that Ad5-EMC6 impairs the tumorigenesis of SGC7901 gastric cancer cells in nude mice. Additionally, Ad5-EMC6 enhances the sensitivity of gastric cancer cells to the chemotherapeutic drug etoposide. Collectively, these results demonstrate that EMC6-induced apoptosis of gastric cancer cells occurs at least partially through the mitochondrial-mediated apoptosis pathway. Our study suggests a rational basis for the potential clinical application of Ad5-EMC6 in gastric cancer. (C) 2019 Elsevier Inc. All rights reserved.