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Review
, 282 (1), 1-8

Helicobacter Pylori Virulence Factors in Gastric Carcinogenesis

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Review

Helicobacter Pylori Virulence Factors in Gastric Carcinogenesis

Sicheng Wen et al. Cancer Lett.

Abstract

Helicobacter pylori infection is the most important risk factor in the development of non-cardia gastric adenocarcinoma; host genetic variability and dietary co-factors also modulate risk. Because most H. pylori infections do not cause cancer, H. pylori heterogeneity has been investigated to identify possible virulence factors. The strongest candidates are genes within the cag (cytotoxin-associated antigen) pathogenicity island, including the gene encoding the CagA protein, as well as polymorphic variation in the VacA vacuolating exotoxin and the blood group antigen binding adhesin BabA. Improved understanding of the pathogenesis of H. pylori-associated gastric cancer may improve risk stratification for prevention and therapy.

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Conflicts of interest Statement

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The pathogenesis of H. pylori infection. Virulence factors such as CagA, genes within the cag PAI, VacA, BabA and SabA are involved in numerous host cell effects. H. pylori adherence to gastric epithelial cells is mediated by BabA and SabA binding Lewisb, and Lewisx/a respectively, thus facilitating H. pylori colonization and the efficient delivery of virulence factors to host cells. Following the attachment of H. pylori to gastric epithelial cell, the CagA protein is delivered into gastric epithelial cells through the H. pylori type 4 secretion system (T4SS). There, CagA may be tyrosine phosphorylated at EPIYA sites initially by SRC and in more sustained fashioned by ABL kinases. CagA can interact with intracellular proteins and deregulate distinct signaling pathways through both tyrosine phosphorylation-dependent or independent mechanisms. The pathobiological effects including cell elongation (producing cell scattering and the “hummingbird” phenotype), disruption of intercellular junctions, loss of cell polarity, the promotion of inflammation and dysregulation of proliferation and apoptosis. The effects of VacA on host cells include induction of cytoplasmic vacuolation, mitochondrial damage, cytochrome c release, apoptosis and immune evasion. Many of these events may contribute to gastric carcinoma development.

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