title: 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.
authors.affiliation: Bacteriology Laboratory, University of Bordeaux, Bordeaux, France.|INSERM, U853, Bordeaux, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Bessède
authors.affiliation: Bacteriology Laboratory, University of Bordeaux, Bordeaux, France.|INSERM, U853, Bordeaux, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Molina
authors.affiliation: Bacteriology Laboratory, University of Bordeaux, Bordeaux, France.|INSERM, U853, Bordeaux, France.
authors.forename: Luis
authors.initials: L
authors.lastname: Acuña-Amador
authors.affiliation: EA2406 Histologie et Pathologie Moléculaire des Tumeurs, University of Bordeaux, Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Dubus
authors.affiliation: 'RNA: Natural and Artificial Regulation' (ARNA) Laboratory, University of Bordeaux, Bordeaux, France.|INSERM, U869, Bordeaux, France.
authors.forename: Cathy
authors.initials: C
authors.lastname: Staedel
authors.affiliation: Bacteriology Laboratory, University of Bordeaux, Bordeaux, France.|INSERM, U853, Bordeaux, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Chambonnier
authors.affiliation: Bacteriology Laboratory, University of Bordeaux, Bordeaux, France.|INSERM, U853, Bordeaux, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Buissonnière
authors.affiliation: Bacteriology Laboratory, University of Bordeaux, Bordeaux, France.|INSERM, U853, Bordeaux, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Sifré
authors.affiliation: EA2406 Histologie et Pathologie Moléculaire des Tumeurs, University of Bordeaux, Bordeaux, France.|Experimental Pathology Platform, SIRIC BRIO, University of Bordeaux, Bordeaux, France.
authors.forename: Alban
authors.initials: A
authors.lastname: Giese
authors.affiliation: Bacteriology Laboratory, University of Bordeaux, Bordeaux, France.|INSERM, U853, Bordeaux, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Bénéjat
authors.affiliation: Service Commun des Animaleries, Animalerie A2, University of Bordeaux, Bordeaux, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Rousseau
authors.affiliation: Service Commun des Animaleries, Animalerie Transgénique, University of Bordeaux, Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Costet
authors.affiliation: Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Sacks
authors.affiliation: Bacteriology Laboratory, University of Bordeaux, Bordeaux, France.|INSERM, U853, Bordeaux, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Mégraud
authors.affiliation: Bacteriology Laboratory, University of Bordeaux, Bordeaux, France.|INSERM, U853, Bordeaux, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Varon
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D018960:Hyaluronan Receptors / Q000378:metabolism; D006965:Hyperplasia; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D010641:Phenotype; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D013997:Time Factors; D020703:ras GTPase-Activating Proteins / Q000172:deficiency* / Q000235:genetics
chemical_list: D015820:Cadherins; C476399:Cd44 protein, mouse; C000611838:Cdh1 protein, mouse; D018960:Hyaluronan Receptors; C101203:IQ motif containing GTPase activating protein 1; D020703:ras GTPase-Activating Proteins
keywords: CD44; E-cadherin; EMT; Zeb; gastric cancer