Contributors: Pathogenèse de Helicobacter - Helicobacter Pathogenesis; Institut Pasteur Paris (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS); Institut Cochin (IC UM3 (UMR 8104 / U1016)); Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Institut de Génétique et Développement de Rennes (IGDR); Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique); Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT); Institut Pasteur Paris (IP); Pathogénie des infections systémiques (Inserm U1002); Neuropathologie expérimentale - Experimental neuropathology; Institut Pasteur Paris (IP)-Université Paris Descartes - Paris 5 (UPD5); AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement; Instituto Mexicano del Seguro Social Mexico City, Mexico (IMSS); Università degli Studi di Firenze = University of Florence = Université de Florence (UniFI); Institut Mutualiste de Montsouris (IMM); Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou; Université Paris Diderot; Ligue Contre le Cancer; Odyssey Reinsurance Company; FIS/IMSS/PROT/PRIO/13/027), Fondo de Investigacion en salud, IMSS, Mexico; West committee Ligue Nationale Contre le Cancer; UMS Biosit; We thank Sophie Vaulont (Institut Cochin, Paris, France) for Usf1-/- mice, Timothy C Wang (Columbia University, NY, USA) for providing us couples of INS-GAS mice and Joana Gomes and Celso Reis (I3S-IPATIMUP, Porto, Portugal) for MKN45 cells. We also thank Laurence Bernard-Touami and the Animal Housing ARCHE (UMS Biosit, https://biosit.univ-rennes1.fr, University of Rennes, France), and David Hardy and Magalie Tichit (Unit of Experimental Neuropathology, Institut Pasteur, Paris, France) for her technical help on the histology part and the UtechS Photonic BioImaging (Imagopole), C2RT, Institut Pasteur, supported by the French National Research Agency (France BioImaging; ANR-10–INSB–04; Investments for the Future), both as a part of the FranceBioImaging infrastructure.; ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010)
نبذة مختصرة : International audience ; Objective - Design - Human gastric epithelial cell lines were infected with 7.13, exposed or not to a DNA-damaging agent camptothecin (CPT), to mimic a genetic instability context. We quantified the expression of , and their target genes, we determined their subcellular localisation by immunofluorescence and examined USF1/p53 interaction. and INS-GAS mice were used to strengthen the findings in vivo and patient data examined for clinical relevance. Results - In vivo we revealed the dominant role of USF1 in protecting gastric cells against -induced carcinogenesis and its impact on p53 levels. In vitro, delocalises USF1 into foci close to cell membranes. prevents USF1/p53 nuclear built up and relocates these complexes in the cytoplasm, thereby impairing their transcriptional function. also inhibits CPT-induced USF1/p53 nuclear complexes, exacerbating CPT-dependent DNA damaging effects. Conclusion - Our data reveal that the depletion of USF1 and its de-localisation in the vicinity of cell membranes are essential events associated to the genotoxic activity of infection, thus promoting gastric carcinogenesis. These findings are also of clinical relevance, supporting USF1 expression as a potential marker of GC susceptibility.
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