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Deletion of IQGAP1 promotes Helicobacter pylori -induced gastric dysplasia in mice and acquisition of cancer stem cell properties in vitro

Abstract : Helicobacter pylori infection is responsible for gastric carcinogenesis but host factors are also implicated. IQGAP1, a scaffolding protein of the adherens junctions interacting with E-cadherin, regulates cellular plasticity and proliferation. In mice, IQGAP1 deficiency leads to gastric hyperplasia. The aim of this study was to elucidate the consequences of IQGAP1 deletion on H. pylori-induced gastric carcinogenesis.Transgenic mice deleted for iqgap1 and WT littermates were infected with Helicobacter sp., and histopathological analyses of the gastric mucosa were performed. IQGAP1 and E-cadherin expression was evaluated in gastric tissues and in gastric epithelial cell lines in response to H. pylori infection. The consequences of IQGAP1 deletion on gastric epithelial cell behaviour and on the acquisition of cancer stem cell (CSC)-like properties were evaluated. After one year of infection, iqgap1+/- mice developed more preneoplastic lesions and up to 8 times more gastro-intestinal neoplasia (GIN) than WT littermates. H. pylori infection induced IQGAP1 and E-cadherin delocalization from cell-cell junctions. In vitro, knock-down of IQGAP1 favoured the acquisition of a mesenchymal phenotype and CSC-like properties induced by H. pylori infection.Our results indicate that alterations in IQGAP1 signalling promote the emergence of CSCs and gastric adenocarcinoma development in the context of an H. pylori infection.
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Emilie Bessède, Silvia Molina, Luis Acuña Amador, Pierre Dubus, Cathy Staedel, et al.. Deletion of IQGAP1 promotes Helicobacter pylori -induced gastric dysplasia in mice and acquisition of cancer stem cell properties in vitro. Oncotarget, Impact journals, 2016, 7 (49), pp.80688-80699. ⟨10.18632/oncotarget.12486⟩. ⟨inserm-03004873⟩

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