Helicobacter pylori regulates cellular migration and apoptosis by activation of phosphatidylinositol 3-kinase signaling.
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.
Nagy
Toni A
TA
Division of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Frey
Mark R
MR
Yan
Fang
F
Israel
Dawn A
DA
Polk
D Brent
DB
Peek
Richard M
RM
D017209:Apoptosis / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000382:microbiology / Q000502:physiology*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013270:Stomach / Q000166:cytology
D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt