The human microbial pathogen Helicobacter pylori colonises the stomach of more than half of the worlds population. The microorganism can induce chronic gastritis, peptic ulceration and more rarely, gastric adenocarcinoma. Highly virulent H. pylori strains carry a cag pathogenicity island (cag PAI), which encodes proteins involved in a specialised type IV secretion system (T4SS). H. pylori induces T4SS-dependent and -independent processes by which H. pylori takes direct command of gastric epithelial cell signaling. The H. pylori effector protein cytotoxin associated gene A (CagA), which is translocated via the T4SS into epithelial cells, contributes to the modulation of cellular functions. In addition, H. pylori transactivates the EGFR, a process involving inter-receptor cross talk and extracellular ADAM metalloproteinase cleavage of membrane bound EGFR ligands. The multiple signal transduction pathways activated during H. pylori infection lead to a complex series of events promoting inappropriate inflammatory responses, epithelial hyperproliferation, epithelial survival and transformation. The H. pylori induced epithelial cellular changes, as well as chemopreventative therapeutic strategies, will be introduced in this review.
Keywords: Helicobacter pylori, CagA, epithelial proliferation, NF-kB, EGFR, ADAM metalloproteinases, c-Met
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