ArticleGastroenterology2010
Helicobacter pylori infection promotes methylation and silencing of trefoil factor 2, leading to gastric tumor development in mice and humans.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 150 citations in OpenAlex.
- AURKA regulates LGR5 in response to Helicobacter Pylori infection by modulating its deubiquitination.Cell death and differentiation · 2026Article
- Conventional and Novel Approaches to Establishing Mouse Models of Gastric Cancer in the Past, Present, and Potential Post-H. Pylori Infection Era.Biological procedures online · 2026Review
- Identification of LGR5 and TFF2 as Biomarkers in High-Risk Chronic Atrophic Gastritis: From Multi-Omics Mining to Clinical Validation.Digestion · 2026Article
- Serum TFF2 as a more reliable biomarker for gastric cancer and early gastric cancer: a cross-sectional population-based study.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- A CXCR4 partial agonist improves immunotherapy by targeting immunosuppressive neutrophils and cancer-driven granulopoiesis.Cancer cell · 2025Article
- Long-term memory in epithelia: transient IFNγ exposure drives stable repression of TFF1 in gastric epithelial cells via epigenetic changes.Frontiers in immunology · 2025Article
- Helicobacter Pylori-induced BRD2 mInternational journal of biological sciences · 2025Article
- SOX9 is regulated by AURKA in response to Helicobacter pylori infection via EIF4E-mediated cap-dependent translation.Cancer letters · 2024Article
- Review
- Organoid-Based Human Stomach Micro-Physiological System to Recapitulate the Dynamic Mucosal Defense Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Prognostic biomarkers and molecular pathways mediating Helicobacter pylori-induced gastric cancer: a network-biology approach.Genomics & informatics · 2023Article
- Review
- Helicobacter pylori-induced RASAL2 Through Activation of Nuclear Factor-κB Promotes Gastric Tumorigenesis via β-catenin Signaling Axis.Gastroenterology · 2022Article
- Evaluation of mutagenesis, necrosis and apoptosis induced by omeprazole in stomach cells of patients with gastritis.Cancer cell international · 2022Article
- IL-33 promotes gastric tumour growth in concert with activation and recruitment of inflammatory myeloid cells.Oncotarget · 2022Article
- Trefoil Factor Family (TFF) Peptides and Their Links to Inflammation: A Re-evaluation and New Medical Perspectives.International journal of molecular sciences · 2021Review
- The Role of Host Cell DNA Methylation in the Immune Response to Bacterial Infection.Frontiers in immunology · 2021Review
- Induction and Prevention of Gastric Cancer with CombinedCancers · 2020Article
- MUC1 is associated with TFF2 methylation in gastric cancer.Clinical epigenetics · 2020Article
- Core 1-derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer.The Journal of experimental medicine · 2020Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsTrefoil factors (TFFs) regulate mucosal repair and suppress tumor formation in the stomach. Tff1 deficiency results in gastric cancer, whereas Tff2 deficiency increases gastric inflammation. TFF2 expression is frequently lost in gastric neoplasms, but the nature of the silencing mechanism and associated impact on tumorigenesis have not been determined.
methodsWe investigated the epigenetic silencing of TFF2 in gastric biopsy specimens from individuals with Helicobacter pylori-positive gastritis, intestinal metaplasia, gastric cancer, and disease-free controls. TFF2 function and methylation were manipulated in gastric cancer cell lines. The effects of Tff2 deficiency on tumor growth were investigated in the gp130(F/F) mouse model of gastric cancer.
resultsIn human tissue samples, DNA methylation at the TFF2 promoter began at the time of H pylori infection and increased throughout gastric tumor progression. TFF2 methylation levels were inversely correlated with TFF2 messenger RNA levels and could be used to discriminate between disease-free controls, H pylori-infected, and tumor tissues. Genome demethylation restored TFF2 expression in gastric cancer cell lines, so TFF2 silencing requires methylation. In Tff2-deficient gp130(F/F)/Tff2(-/-) mice, proliferation of mucosal cells and release of T helper cell type-1 (Th-1) 1 cytokines increased, whereas expression of gastric tumor suppressor genes and Th-2 cytokines were reduced, compared with gp130(F/F)controls. The fundus of gp130(F/F)/Tff2(-/-) mice displayed glandular atrophy and metaplasia, indicating accelerated preneoplasia. Experimental H pylori infection in wild-type mice reduced antral expression of Tff2 by increased promoter methylation.
conclusionsTFF2 negatively regulates preneoplastic progression and subsequent tumor development in the stomach, a role that is subverted by promoter methylation during H pylori infection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.