ArticlePloS one2012
Reduced surface expression of epithelial E-cadherin evoked by interferon-gamma is Fyn kinase-dependent.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
23 citing papers in PubMed, 35 citations in OpenAlex.
- Identification of proliferating CD103Virchows Archiv : an international journal of pathology · 2026Article
- Pro-Inflammatory Cytokines as Core Mediators of Colonic Epithelial Barrier Dysfunction: Roles of TNF-α, IFN-γ, IL-1β, and IL-6.International journal of molecular sciences · 2026Review
- Mucosal Responses to Type II Interferon in IBD.Inflammatory bowel diseases · 2025Article
- Beyond destruction: emerging roles of the E3 ubiquitin ligase Hakai.Cellular & molecular biology letters · 2025Review
- Disruption of Epithelial Barrier Integrity via Altered GILZ/c-Rel/RACK1 Signaling in Inflammatory Bowel Disease.Journal of Crohn's & colitis · 2025Article
- An Engineered Probiotic Produces a Type III Interferon IFNL1 and Reduces Inflammations inACS biomaterials science & engineering · 2023Article
- Understanding disruption of the gut barrier during inflammation: Should we abandon traditional epithelial cell lines and switch to intestinal organoids?Frontiers in immunology · 2023Review
- Interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer.Scientific reports · 2022Article
- Inflammation Mediates the Development of Aggressive Breast Cancer Following Radiotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- theLiTE™: A Screening Platform to Identify Compounds that Reinforce Tight Junctions.Frontiers in pharmacology · 2021Review
- A Novel Pharmacological Approach to Enhance the Integrity and Accelerate Restitution of the Intestinal Epithelial Barrier.Inflammatory bowel diseases · 2020Article
- HPV Induces Changes in Innate Immune and Adhesion Molecule Markers in Cervical Mucosa With Potential Impact on HIV Infection.Frontiers in immunology · 2020Article
- The elusive case of human intraepithelial T cells in gut homeostasis and inflammation.Nature reviews. Gastroenterology & hepatology · 2018Review
- The role of ubiquitination and deubiquitination in the regulation of cell junctions.Protein & cell · 2018Review
- The Superantigen Toxic Shock Syndrome Toxin 1 Alters Human Aortic Endothelial Cell Function.Infection and immunity · 2018Article
- Therapy-induced E-cadherin downregulation alters expression of programmed death ligand-1 in lung cancer cells.Lung cancer (Amsterdam, Netherlands) · 2017Article
- Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms.Biochimica et biophysica acta. Molecular cell research · 2017Review
- Adherens Junction and E-Cadherin complex regulation by epithelial polarity.Cellular and molecular life sciences : CMLS · 2016Review
- E-cadherin Is Important for the Maintenance of Intestinal Epithelial Homeostasis Under Basal and Inflammatory Conditions.Digestive diseases and sciences · 2015Article
- An emerging role of the cellular prion protein as a modulator of a morphogenetic program underlying epithelial-to-mesenchymal transition.Frontiers in cell and developmental biology · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Interferon gamma (IFNγ) is an important regulatory cytokine that can exert a pro-inflammatory effect in the gut, where it has been shown to increase epithelial permeability via disruption of the tight junctions. Here we investigated the potential for IFNγ to regulate the adherens junction protein E-cadherin, an important mediator of normal epithelial tissue function, using the model T84 human colonic epithelial cell line. IFNγ (10 ng/ml) stimulated increased internalization of E-cadherin as assessed by immunofluorescence microscopy; internalization was reversed when cells were treated with PP1 (125 nM), a Src kinase-selective inhibitor. Immunoprecipitation studies demonstrated loss of E-cadherin from membrane fractions following IFNγ treatment and a corresponding increase in cytosolic E-cadherin and its binding partners, p120-catenin and beta-catenin: effects that were Src-kinase dependent. E-cadherin and p120-catenin phosphorylation was increased by IFNγ treatment and siRNA studies showed this was dependent upon the Src-kinase isoform Fyn. E-cadherin ubiquitinylation and subsequent proteasomal degradation stimulated by IFNγ was found to be dependent upon Fyn and the E-cadherin-selective ubiquitin ligase, Hakai. Use of Fyn and Hakai siRNA inhibited the internalization of E-cadherin as shown by immunoblotting and confocal fluorescence microscopy. Finally, IFNγ treatment resulted in a more fragile T84 cell monolayer with increased cell detachment in response to physical stress, which was prevented by PP1 and siRNA targeting Fyn or Hakai. Collectively, these results demonstrate a Fyn kinase-dependent mechanism through which IFNγ regulates E-cadherin stability and suggest a novel mechanism of disruption of epithelial cell contact, which could contribute to perturbed epithelial barrier function.
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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.