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.