Nagy Toni A, Frey Mark R, Yan Fang, Israel Dawn A, Polk D Brent, Peek Richard M
Division of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
J Infect Dis. 2009 Mar 1;199(5):641-51. doi: 10.1086/596660.
Helicobacter pylori is the strongest identified risk factor for gastric adenocarcinoma. One H. pylori virulence constituent that augments cancer risk is the cag secretion system, which translocates CagA and peptidoglycan into host cells, eventuating in activation of signal transduction pathways. AKT is a target of phosphatidylinositol 3-kinase (PI3K) and is activated in gastric cancer, but the relationship between PI3K-AKT and H. pylori-induced cellular responses with carcinogenic potential remains unclear. We defined the molecular pathways mediating H. pylori-stimulated AKT activation and the biological consequences of these events in gastric epithelial cells. H. pylori enhanced PI3K-AKT signaling in a Src- and epidermal growth factor receptor-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 migration. These results indicate that PI3K-AKT signaling regulates pathophysiologic responses to H. pylori that may lower the threshold for carcinogenesis.
幽门螺杆菌是已确定的胃腺癌最强风险因素。一种增加癌症风险的幽门螺杆菌毒力成分是cag分泌系统，它将CagA和肽聚糖转运到宿主细胞中，最终导致信号转导通路的激活。AKT是磷脂酰肌醇3激酶（PI3K）的一个靶点，在胃癌中被激活，但PI3K-AKT与幽门螺杆菌诱导的具有致癌潜力的细胞反应之间的关系仍不清楚。我们确定了介导幽门螺杆菌刺激的AKT激活的分子途径以及这些事件在胃上皮细胞中的生物学后果。幽门螺杆菌以Src和表皮生长因子受体依赖的方式增强PI3K-AKT信号传导，这也由功能性cag分泌系统和肽聚糖介导。PI3K激活减弱了感染后的细胞凋亡，并且是幽门螺杆菌诱导细胞迁移所必需的。这些结果表明，PI3K-AKT信号传导调节对幽门螺杆菌的病理生理反应，这可能会降低致癌阈值。
