ArticleGastroenterology2008
Intestinal deletion of Pofut1 in the mouse inactivates notch signaling and causes enterocolitis.
Article in Gastroenterology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 80 citations in OpenAlex.
- UC-associated autoantibodies to αvβ6 inhibit mucosal TGFβ activation and predispose to intestinal inflammation.bioRxiv : the preprint server for biology · 2026Article
- Structure, function, and implications of fucosyltransferases in health and disease.Nature communications · 2025Review
- Fucosylation in digestive inflammatory diseases and cancers: From mechanical studies to clinical translation.Genes & diseases · 2025Review
- EOGT enables residual Notch signaling in mouse intestinal cells lacking POFUT1.Scientific reports · 2023Article
- Glycans that regulate Notch signaling in the intestine.Biochemical Society transactions · 2022Review
- Article
- POFUT1 acts as a tumor promoter in glioblastoma by enhancing the activation of Notch signaling.Journal of bioenergetics and biomembranes · 2021Article
- GOLM1 restricts colitis and colon tumorigenesis by ensuring Notch signaling equilibrium in intestinal homeostasis.Signal transduction and targeted therapy · 2021Article
- Molecular characterization of colorectal adenomas reveals POFUT1 as a candidate driver of tumor progression.International journal of cancer · 2020Article
- POFUT1 is dispensable for structure, function and survival of mouse podocytes.American journal of translational research · 2020Article
- PLAGL2 and POFUT1 are regulated by an evolutionarily conserved bidirectional promoter and are collaboratively involved in colorectal cancer by maintaining stemness.EBioMedicine · 2019Article
- Multiple roles for O-glycans in Notch signalling.FEBS letters · 2018Review
- POFUT1 promotes colorectal cancer development through the activation of Notch1 signaling.Cell death & disease · 2018Article
- Epithelial Hes1 maintains gut homeostasis by preventing microbial dysbiosis.Mucosal immunology · 2018Article
- C3orf21 ablation promotes the proliferation of lung adenocarcinoma, and its mutation at the rs2131877 locus may serve as a susceptibility marker.Oncotarget · 2017Article
- Epithelial Cell Inflammasomes in Intestinal Immunity and Inflammation.Frontiers in immunology · 2017Review
- Alteration of colonic epithelial cell differentiation in mice deficient for glucosaminyl N-deacetylase/N-sulfotransferase 4.Oncotarget · 2016Article
- Reg4+ deep crypt secretory cells function as epithelial niche for Lgr5+ stem cells in colon.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Stem Cells in the Intestine: Possible Roles in Pathogenesis of Irritable Bowel Syndrome.Journal of neurogastroenterology and motility · 2016Review
- Notch signalling regulates asymmetric division and inter-conversion between lgr5 and bmi1 expressing intestinal stem cells.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsNotch downstream targets are fundamental to intestinal cell lineage commitment and are suggested as therapeutic targets for colon cancer cells. However, the role of endogenous Notch signaling through receptor-ligand interaction, and effects of its longer term down-regulation on intestinal homeostasis, are unclear.
methodsTo address these issues, the gene encoding protein O-fucosyltransferase 1, an enzyme required for Notch ligand binding and thus activation of all Notch receptors, was deleted in the mouse intestinal and colonic epithelium, through Villin-Cre-mediated recombination.
resultsPofut1 deletion inactivated Notch signaling, giving rise to smaller but viable mice. These mice exhibited a large increase in all intestinal secretory cell lineages, which accumulated in the crypts, resulting in crypt hyperplasia. Although proliferating cells were largely reduced in the colon, the transit amplifying compartment was maintained in the upper crypts of the intestinal mucosa. By 9 months, these perturbations in cell maturation altered mucus-associated gut microbiota and caused chronic intestinal inflammation, with evidence of bacterial translocation to the mesenteric lymph nodes, macrophage, and T-lymphocyte infiltration, and Th1/Th17 immune response. Dysplastic foci were also observed in Pofut1-deficient small intestine with occasional progression to tumor formation.
conclusionsMucus hypersecretion upon Pofut1 inactivation is accompanied by alteration of the mucus-associated flora, which likely contributes to the development of enterocolitis. Therefore, these data identify important potential complications in strategies to target Notch signaling in therapeutic approaches to colon cancer.
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Registered trials
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