New study explains how inflammation causes gastric cancer

(Kanazawa University) Researchers from Kanazawa University and the Japan Agency for Medical Research and Development have solved the decades-old mystery of how stomach bacterium Helicobacter pylori causes gastric cancer. Using mouse models and human cancer cell lines, they showed that inflammation resulting from bacterial infection leads to the proliferation of gastric epithelial cells, which ultimately form gastric tumors. By blocking the protein pathway responsible for this proliferation, they prevented gastric tumor formation.
Source: EurekAlert! - Biology - Category: Biology Source Type: news

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Abstract Helicobacter pylori infection always induces gastritis, which may progress to ulcer disease or cancer. The mechanisms underlying mucosal injury by the bacteria are incompletely understood. Here we identify a novel pathway for H. pylori-induced gastric injury, the impairment of maturation of the essential transport enzyme and cell adhesion molecule, Na,K-ATPase. The Na,K-ATPase is comprised of α and β subunits that assemble in the ER prior to trafficking to the plasma membrane. Attachment of H. pylori to gastric epithelial cells increased Na,K-ATPase ubiquitylation, decreased its surface and tot...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research
Conclusion. Residues 303-456 of the N-terminal region of CagA induce IL-8 production via a CagA303-456-ITGB1-p38-IL-8 pathway, and ERK1/2 is also involved in the release of IL-8. Extracellular CagA might induce IL-8 production before translocation into AGS cells. PMID: 32100714 [PubMed - as supplied by publisher]
Source: Journal of Medical Microbiology - Category: Microbiology Authors: Tags: J Med Microbiol Source Type: research
Authors: Bussière FI, Michel V, Fernandes J, Costa L, Camilo V, Nigro G, De Reuse H, Fiette L, Touati E Abstract Helicobacter pylori infection causes chronic gastritis and is the major risk factor of gastric cancer. H. pylori induces a chronic inflammation-producing reactive oxygen species (ROS) which is a source of chromosome instabilities and contributes to the development of malignancy. H. pylori also promotes DNA hypermethylation, known to dysregulate essential genes that maintain genetic stability. The maintenance of telomere length by telomerase is essential for chromosome integrity. Telomerase reverse...
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
CagA gene transduction increases KLF4 promoter methylation level, which leads to inactivation of KLF4. Helicobacter pylori infection leads to KLF4 inactivation in gastric cancer through a TET1 ‐mediated DNA methylation mechanism. AbstractKr üppel‐like factor 4 (KLF4) has a tumor suppressor role in the progression of gastric cancer (GC), and inhibition or loss of KLF4 expression was identified in GC. The aim of this study was to explore the new molecular mechanism of KLF4 inactivation in gastric cancer. Herein, we report thatHelicobacter pylori infection or Cag pathogenicity island protein A (CagA) gene transductio...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
The main risk factor for stomach cancer, the third most common cause of cancer death worldwide, is infection with Helicobacter pylori bacterial strains that inject cytotoxin-associated gene A (CagA). As the first described bacterial oncoprotein, CagA causes gastric epithelial cell transformation by promoting an epithelial-to-mesenchymal transition (EMT)-like phenotype that disrupts...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: PNAS Plus Source Type: research
This study investigated the molecular targets of the component herbs of QLSP in preventing precancerous lesions based on network pharmacology. Network pharmacology analysis revealed that the 6 herbs regulated multiple CAG-related genes, among which the most important were cancer-related pathway (apoptosis, p53, and VEGF) and epithelial cell signaling in Helicobacter pylori infection. Further animal experiments showed that the expression of survivin and p53 in precancerous lesions of CAG rats was significantly increased which was suppressed by QLSP. Moreover, telomerase activity was inhibited in precancerous lesions of CAG ...
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
meyer Cortactin is an actin binding protein and actin nucleation promoting factor regulating cytoskeletal rearrangements in nearly all eukaryotic cell types. From this perspective, cortactin poses an attractive target for pathogens to manipulate a given host cell to their own benefit. One of the pathogens following this strategy is Helicobacter pylori, which can cause a variety of gastric diseases and has been shown to be the major risk factor for the onset of gastric cancer. During infection of gastric epithelial cells, H. pylori hijacks the cellular kinase signaling pathways, leading to the disruption of key cell fun...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Authors: Zhang F, Chen C, Hu J, Su R, Zhang J, Han Z, Chen H, Li Y Abstract Helicobacter pylori (H. pylori) is a gram-negative pathogen that colonizes gastric epithelial cells. The drug resistance rates of H. pylori have dramatically increased, causing persistent infections. Chronic infection by H. pylori is a critical cause of gastritis, peptic ulcers and even gastric cancer. In host cells, autophagy is stimulated to maintain cellular homeostasis following intracellular pathogen recognition by the innate immune defense system. However, H. pylori-induced autophagy is not consistent during acute and chronic infectio...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Abstract Chronic infection with Helicobacter pylori cagA-positive strains is the strongest risk factor for gastric cancer. The cagA gene product, CagA, is delivered into gastric epithelial cells via the bacterial type IV secretion system. Delivered CagA then undergoes tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in its C-terminal region and acts as an oncogenic scaffold protein that physically interacts with multiple host signaling proteins in both tyrosine phosphorylation-dependent and -independent manners. Analysis of CagA using in vitro cultured gastric epithelial cells has indicated that ...
Source: Cellular and Molecular Immunology - Category: Molecular Biology Authors: Tags: Cell Mol Immunol Source Type: research
This study could provide usher in a new opportunity to understand the role of less studied gastric bacteria in the development of gastric diseases.
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
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