CagA Associates with c-Met, E-Cadherin, and p120-Catenin in a Multiproteic Complex That Suppresses Helicobacter pylori-Induced Cell-Invasive Phenotype

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Oliveira MJ (Author) Other; Costa AM (Author) FMUP; Costa AC (Author) Other; Ferreira R (Author) FMUP; Sampaio P (Author) Other; Machado JC (Author) FMUP; Seruca R (Author) Other; Mareel M (Author) Other; Figueiredo C (Author) FMUP

Journal

Title: Journal of Infectious Diseases

Vol. 200

Pages: 745-755

ISSN: 0022-1899

Publisher: Oxford University Press

Indexing

ISI Web of Knowledge - 78 Citations

Scopus - 79 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: P-003-G8P

DOI: 10.1086/604727

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11