Journal
ONCOTARGET
Volume 7, Issue 49, Pages 80688-80699Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.12486
Keywords
EMT; gastric cancer; CD44; E-cadherin; Zeb
Categories
Funding
- French 'Association pour la Recherche contre le Cancer' [8412]
- Institut National du Cancer [07/3D1616/IABC-23-12/NC-NG]
- Conseil Regional d'Aquitaine [20071301017, 20081302203]
- SIRIC BRIO (Site de Recherche Integree sur le Cancer -Bordeaux Recherche Integree Oncologie) [INCa-DGOS-Inserm 6046]
- National Institutes of Health Intramural Research Program
Ask authors/readers for more resources
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 gastrointestinal 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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available