幽门螺杆菌通过激活磷脂酰肌醇3-激酶信号来调节细胞迁移

Helicobacter pylori regulates cellular migration and apoptosis by activation of phosphatidylinositol 3-kinase signaling

目的幽门螺杆菌被认为是诱发胃癌的最强的风险因素。幽门螺旋杆菌的毒性成分是可以增加癌症危险的cag分泌系统,它可以使cagA和肽聚糖易位进入宿主细胞,进而激活信号转导通路。AKT是磷脂酰肌醇3-激酶(PI3K)的目的蛋白,并在胃癌中被激活,但PI3K-AKT和具有潜在致癌性的幽门螺旋杆菌诱导的细胞反应之间的关系尚不清楚。方法我们揭示了介导幽门螺旋杆菌刺激的AKT活化和胃上皮细胞的这些生物学结果之间的分子通路。结果幽门螺旋杆菌以Scr和表皮生长因子受体依赖性方式增加PI3K-AKT的信号,是幽门螺旋杆菌诱导的细胞迁移不可或缺的。结论这些结果表明,PI3K-AKT信号调节幽门螺旋杆菌诱发的病理生理反应,从而降低癌变门槛。

Objective Helicobacter pylori was the strongest identified risk factor for gastric adenocarcinoma. One H. pylori virulence constituent that augments cancer risk was the cag secretion system, which translocates cagA and peptidoglycan into host cells, eventuating in activation of signal transduction pathways. AKT was a target of phos- phatidylinositol 3-kinase （PI3K） and was activated in gastric cancer, but the relationship between PI3K-AKT and H. pylori - induced cellular responses with carcinogenic potential remains unclear. Methods We defined the mo- lecular pathways mediating H. pylori - stimulated AKT activation and the biological consequences of these events in gastric epithelial cells. Results H. pylori enhanced PI3K-AKT signaling in a Src- and epidermal growth factor re- ceptor - dependent manner, which was also mediated by a functional cag secretion system and peptidoglycan. PI3K activation attenuated apoptosis in response to infection and was required for H. pylori - induced cell migra- tion. Conelusion These results indicate that PI3K-AKT signaling regulates pathophysiologic responses to H. pylori that may lower the threshold for carcinogenesis.