Helicobacter Pylori-induced DNA Double Strand Breaks And Gastric Cancer
Abstract
Helicobacter pylori is a bacterial pathogen that colonizes the human gastric mucosa and contributes to the pathogenesis of gastric cancer. H. pylori infection induces DNA double-strand breaks (DSBs) in gastric epithelial cells, which compromise host cell genomic integrity. While the genotoxicity of H. pylori clearly promotes gastric carcinogenesis in infected individuals, the underlying molecular mechanisms behind this process are not fully understood. In this study, we have shown that H. pylori induces DNA DSBs in human gastric adenocarcinoma (AGS) cells through NF-B activation. Inhibition of NF-B in AGS cells by the expression of N-I-B, a degradation-resistant mutant of I-B (inhibitor of NF-B), dramatically reduces H. pylori-induced DNA DSBs. We further showed that the H. pylori type IV secretion system and the H. pylori virulence factor, CagA, but not VacA, were required for inducing DNA DSBs in the infected AGS cells. Our results strongly support the notion that H. pylori infection triggers CagA-mediated NF-B activation, which, in turn, promotes DNA DSBs. Current efforts focus on testing the hypothesis that NF-B activation by CagA leads to the accumulation of R-loops, leading to DSBs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2021
- Accession Number
- AD1152340
Entities
People
- Douglas Scott Merrell
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine