CagA associates with c-Met, E-cadherin, and p120-catenin in a multiproteic complex that suppresses Helicobacter pylori-induced cell-invasive phenotype.
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.
Oliveira
Maria Jose
MJ
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.
Costa
Angela Margarida
AM
Costa
Ana Catarina
AC
Ferreira
Rui Manuel
RM
Sampaio
Paula
P
Machado
Jose Carlos
JC
Seruca
Raquel
R
Mareel
Marc
M
Figueiredo
Ceu
C
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
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