title: CagA associates with c-Met, E-cadherin, and p120-catenin in a multiproteic complex that suppresses Helicobacter pylori-induced cell-invasive phenotype.
abstract: BACKGROUND
  Helicobacter pylori induces an invasive phenotype in gastric epithelial cells through a mechanism that requires the type IV secretion system and the phosphorylation of c-Met. The E-cadherin-catenin complex is a major component of the adherens junctions and functions as an invasion suppressor. We investigated whether E-cadherin has a role in H. pylori-induced, c-Met phosphorylation-dependent cell-invasive phenotype.
  
  
  METHODS
  AGS cells that lack E-cadherin and that are invasive to H. pylori stimulation were transduced with E-cadherin and infected with H. pylori. NCI-N87 cells, which endogenously express E-cadherin, were also used for infection experiments.
  
  
  RESULTS
  E-cadherin was sufficient to suppress not only H. pylori-mediated cell-invasive phenotype but also c-Met and p120-catenin tyrosine phosphorylation. H. pylori infection led to increased interactions between E-cadherin and p120-catenin, c-Met and E-cadherin, and c-Met and p120-catenin. Using in vitro infection assays, we showed that H. pylori CagA interacts with E-cadherin, p120-catenin, and c-Met. Finally, using small interfering RNA, we showed that interactions between CagA and E-cadherin and between CagA and p120-catenin were established through c-Met.
  
  
  CONCLUSIONS
  We suggest that H. pylori alters the E-cadherin-catenin complex, leading to formation of a multiproteic complex composed of CagA, c-Met, E-cadherin, and p120-catenin. This complex abrogates c-Met and p120-catenin tyrosine phosphorylation and suppresses the cell-invasive phenotype induced by H. pylori.
authors: Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.
authors: Maria Jose
authors: MJ
authors: Oliveira
authors: Angela Margarida
authors: AM
authors: Costa
authors: Ana Catarina
authors: AC
authors: Costa
authors: Rui Manuel
authors: RM
authors: Ferreira
authors: Paula
authors: P
authors: Sampaio
authors: Jose Carlos
authors: JC
authors: Machado
authors: Raquel
authors: R
authors: Seruca
authors: Marc
authors: M
authors: Mareel
authors: Ceu
authors: C
authors: Figueiredo
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000382:microbiology*; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; C080866:cagA protein, Helicobacter pylori; D019859:Proto-Oncogene Proteins c-met; D000095002:Delta Catenin