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USF1 defect drives p53 degradation during Helicobacter pylori infection and accelerates gastric carcinogenesis

Abstract : 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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Submitted on : Wednesday, December 18, 2019 - 4:08:07 PM
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Lionel Costa, Sébastien Corre, Valérie Michel, Krysten Le Luel, Julien Fernandes, et al.. USF1 defect drives p53 degradation during Helicobacter pylori infection and accelerates gastric carcinogenesis. Gut, BMJ Publishing Group, 2019, pp.gutjnl-2019-318640. ⟨10.1136/gutjnl-2019-318640⟩. ⟨pasteur-02418249⟩

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