ArticleThe Journal of clinical investigation2012
Essential role of gastric gland mucin in preventing gastric cancer in mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 98 citations in OpenAlex.
- Helicobacter pylori cholesteryl α-glucosides contribute to its pathogenicity and immune response by natural killer T cells.PloS one · 2013Trial
- Early-life rotavirus infection susceptibility and later gastrointestinal cancer protection: Reverse antagonistic pleiotropy and potential vaccine benefits.Current research in microbial sciences · 2026Article
- Trefoil factor 2 interacts with A4GNT to regulate inflammation to protect against pneumonia during influenza virus infection.iScience · 2025Article
- Analysis of site-dependent mucins in rat intestinal mucosa using anti-glycan monoclonal antibodies.Glycoconjugate journal · 2025Article
- The gastric microbiome altered by A4GNT deficiency in mice.Frontiers in microbiology · 2025Article
- The Evolution of Extreme Genetic Variability in a Parasite-Resistance Complex.Genome biology and evolution · 2024Article
- The role of gastric mucins and mucin-related glycans in gastric cancers.Cancer science · 2024Review
- Infection and the Glycome─New Insights into Host Response.ACS infectious diseases · 2024Review
- Impaired Glycosylation of Gastric Mucins Drives Gastric Tumorigenesis and Serves as a Novel Therapeutic Target.Gastroenterology · 2024Article
- Marine-Derived Anticancer Agents Targeting Apoptotic Pathways: Exploring the Depths for Novel Cancer Therapies.Marine drugs · 2024Review
- MALDI-TOF MS/MS Analysis of Permethylated O-Glycan Alditols Released from Mucins.Methods in molecular biology (Clifton, N.J.) · 2024Article
- USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis.Frontiers in immunology · 2024Article
- Preparation of O-Glycans from Mucins Using Hydrazine Treatment.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Decreased expression of TFF2 and decreased αGlcNAc glycosylation are malignant biomarkers of pyloric gland adenoma of the duodenum.Scientific reports · 2023Article
- Identification and validation of ferroptosis-related biomarkers and the related pathogenesis in precancerous lesions of gastric cancer.Scientific reports · 2023Article
- A microwell platform for high-throughput longitudinal phenotyping and selective retrieval of organoids.Cell systems · 2023Article
- Artificial intelligence-guided discovery of gastric cancer continuum.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023Article
- Non-Gastro hep advances · 2023Article
- Biology and management of lobular endocervical glandular hyperplasia.The journal of obstetrics and gynaecology research · 2022Review
- α1,4-Linked N-acetylglucosamine suppresses gastric cancer development by inhibiting Mucin-1-mediated signaling.Cancer science · 2022Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides (O-glycans) having terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). Previously, we identified human α1,4-N-acetylglucosaminyltransferase (α4GnT), which is responsible for the O-glycan biosynthesis and characterized αGlcNAc function in suppressing Helicobacter pylori in vitro. In the present study, we engineered A4gnt(-/-) mice to better understand its role in vivo. A4gnt(-/-) mice showed complete lack of αGlcNAc expression in gastric gland mucin. Surprisingly, all the mutant mice developed gastric adenocarcinoma through a hyperplasia-dysplasia-carcinoma sequence in the absence of H. pylori infection. Microarray and quantitative RT-PCR analysis revealed upregulation of genes encoding inflammatory chemokine ligands, proinflammatory cytokines, and growth factors, such as Ccl2, Il-11, and Hgf in the gastric mucosa of A4gnt(-/-) mice. Further supporting an important role for this O-glycan in cancer progression, we also observed significantly reduced αGlcNAc in human gastric adenocarcinoma and adenoma. Our results demonstrate that the absence of αGlcNAc triggers gastric tumorigenesis through inflammation-associated pathways in vivo. Thus, αGlcNAc-terminated gastric mucin plays dual roles in preventing gastric cancer by inhibiting H. pylori infection and also suppressing tumor-promoting inflammation.
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Registered trials
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.