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Helicobacter pylori and gastric carcinogenesis
Open accessAbstract
Gastric carcinoma is the second leading cause of cancer-related deaths in the world, accounting for more than 700,000 deaths each year. Recent studies have revealed that infection with cagA-positive Helicobacter pylori plays an essential role in the development of gastric carcinoma. The cagA-encoded CagA protein is delivered into gastric epithelial cells via the bacterial type IV secretion system, where it undergoes tyrosine phosphorylation by Src and Abl kinases. Tyrosine-phosphorylated CagA then acquires the ability to interact with and deregulate SHP-2 phosphatase, a bona-fide oncoprotein, deregulation of which is involved in a variety of human malignancies. CagA also binds to and inhibits PAR1b/MARK2 polarity-regulating kinase to disrupt tight junctions and epithelial apical-basolateral polarity. These CagA activities may collectively contribute to the transformation of gastric epithelial cells. Indeed, transgenic expression of CagA in mice results in the development of gastrointestinal and hematological malignancies, indicating that CagA is the first bacterial oncoprotein that acts in mammalian cells. The oncogenic potential of CagA may be further potentiated in the presence of chronic inflammation, which aberrantly induces activation-induced cytidine deaminase (AID), a member of the DNA/RNA-editing enzyme family. Ectopically expressed AID may contribute to H. pylori-initiated gastric carcinogenesis by increasing the risk of likelihood of epithelial cells acquiring mutations in cancer-related genes.
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“In addition, when the infection does spread to the oxyntic mucosa, it causes pangastritis, which is associated with hypochloridria, and is responsible for the development of chronic atrophic gastritis, intestinal metaplasia and, finally, dysplasia and GC[69,70].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [70]
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Metadata
- Authors
- Hatakeyama, M.
- Affiliations
- Hokkaido University (JP)
- Corresponding author
- Hatakeyama, Masanori
- ORCID
- Hatakeyama, Masanori
- Venue
- Journal of Gastroenterology
- Published
- 2009-03-07
- Volume
- 44
- Issue
- 4
- Pages
- 239-248
- ISSN
- 0944-1174 (ISSN-L)
- 1435-5922
- OpenAlex
- W2147579496
- Cited by
- 291
- References
- 63
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 13 · 2023: 6 · 2022: 11 · 2021: 11 · 2020: 11 · 2019: 17 · 2018: 8 · 2017: 14 · 2016: 10 · 2015: 15 · 2014: 22 · 2013: 30 · 2012: 16
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science
- Topics
- Health Sciences › Medicine › Gastroenterology › Helicobacter pylori-related gastroenterology studies
- Health Sciences › Medicine › Oncology › Gastric Cancer Management and Outcomes
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Helicobacter pylori, gastric carcinogenesis, gastric cancer, CagA, type IV secretion system, tyrosine phosphorylation, Src kinase, c-Abl, tight junctions, epithelial polarity, chronic inflammation, activation-induced cytidine deaminase, transgenic mouse model, hematologic malignancies
- MeSH terms
- AICDA (Activation-Induced Cytidine Deaminase), Animals, Antigens, Bacterial, Bacterial Proteins, Cytidine Deaminase, Epithelial Cells, Humans, Mice, Transgenic, Mutation, Phosphorylation, Stomach Neoplasms, Helicobacter pylori, Helicobacter Infections, Mice
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