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Review
. 2015:2015:794378.
doi: 10.1155/2015/794378. Epub 2015 Apr 7.

Gastric Carcinogenesis and Underlying Molecular Mechanisms: Helicobacter pylori and Novel Targeted Therapy

Toshihiro Nishizawa  1 , Hidekazu Suzuki  2
Affiliations
Review

Gastric Carcinogenesis and Underlying Molecular Mechanisms: Helicobacter pylori and Novel Targeted Therapy

Toshihiro Nishizawa et al. Biomed Res Int. 2015.

Abstract

The oxygen-derived free radicals that are released from activated neutrophils are one of the cytotoxic factors of Helicobacter pylori-induced gastric mucosal injury. Increased cytidine deaminase activity in H. pylori-infected gastric tissues promotes the accumulation of various mutations and might promote gastric carcinogenesis. Cytotoxin-associated gene A (CagA) is delivered into gastric epithelial cells via bacterial type IV secretion system, and it causes inflammation and activation of oncogenic pathways. H. pylori infection induces epigenetic transformations, such as aberrant promoter methylation in tumor-suppressor genes. Aberrant expression of microRNAs is also reportedly linked to gastric tumorogenesis. Moreover, recent advances in molecular targeting therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2 (HER-2) therapies. This updated review article highlights possible mechanisms of gastric carcinogenesis including H. pylori-associated factors.

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Figures

Figure 1
Figure 1
CagA and major functions. CagA is delivered into gastric epithelial cells via bacterial type IV secretion system. CagA interacts with many signaling molecules that are important for the regulation of cell proliferation, polarity, and motility.
Figure 2
Figure 2
Activation-induced cytidine deaminase (AID) as the DNA/RNA editing enzyme. AID is induced by H. pylori infection and promotes the accumulation of various mutations.
Figure 3
Figure 3
DNA methylation inactivates tumor suppressor genes without gene mutation. Chronic inflammation by H. pylori infection induces aberrant promoter methylation in tumor-suppressor genes.
See this image and copyright information in PMC

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