Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells
Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells
复制标题
Src/caveolin-1调节的EGFR激活拮抗TRAIL诱导的胃癌细胞凋亡
DOI：
10.3892/or.2014.3183
复制
发表时间：
2014-07-01
期刊：
影响因子：
4.2
通讯作者：
Liu, Yunpeng
中科院分区：
文献类型：
--
作者：
Xu, Ling;Qu, Xiujuan;Liu, Yunpeng
胃癌细胞对肿瘤坏死因子相关凋亡诱导配体（TRAIL）不敏感，我们最近发现，脂筏调节的表皮生长因子受体（EGFR）激活拮抗TRAIL诱导的凋亡。然而，目前尚不清楚是否小窝蛋白-1，一个重要的结构组成部分的脂筏，调节脂筏介导的EGFR激活。我们在此报道了TRAIL诱导胃癌细胞SGC-7901和MGC-803中EGFR向脂筏移位并激活。同时，小窝蛋白-1也被激活。敲低小窝蛋白-1部分阻止了EGFR活化并增加了TRAIL敏感性。此外，TRAIL促进Src移位到脂筏和其激活，以及Src与EGFR和小窝蛋白-1的相互作用。Src抑制剂阻止了这些相互作用以及小窝蛋白-1和EGFR的激活，从而增强了TRAIL诱导的细胞凋亡。这些数据表明，Src通过Src-EGFR和Src-caveolin-1的相互作用激活EGFR，然后拮抗TRAIL诱导的胃癌细胞凋亡。
Gastric cancer cells are insensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and we recently showed that lipid raft-regulated epidermal growth factor receptor (EGFR) activation antagonized TRAIL-induced apoptosis. However, it is not clear whether caveolin-1, an essential structural constituent of lipid rafts, regulates lipid raft-mediated EGFR activation. We report here that TRAIL induced the translocation of EGFR into lipid rafts and its activation in gastric cancer SGC-7901 and MGC-803 cells. Simultaneously, caveolin-1 was also activated. Knockdown of caveolin-1 partially prevented EGFR activation and increased TRAIL sensitivity. Moreover, TRAIL promoted the translocation of Src into lipid rafts and its activation, as well as the interaction of Src with both EGFR and caveolin-1. A Src inhibitor prevented these interactions and the activation of caveolin-1 and EGFR, and thus enhanced TRAIL-induced apoptosis. These data suggest that Src activates EGFR through the interaction of both Src-EGFR and Src-caveolin-1, and then antagonizes TRAIL-induced apoptosis in gastric cancer cells.