Helicobacter pylori induces gastric epithelial cell invasion in a c-Met and type IV secretion system-dependent manner

• Tipo: Artigo em Revista Científica Internacional
• Data: 2006

Autores

Oliveira MJ (Autor) Outra; Costa AC (Autor) Outra; Costa AM (Autor) FMUP; Henriques L (Autor) Outra; Suriano G (Autor) Outra; Atherton JC (Autor) Outra; Machado JC (Autor) FMUP; Carneiro F (Autor) FMUP; Seruca R (Autor) Outra; Mareel M (Autor) Outra; Leroy A (Autor) Outra; Figueiredo C (Autor) FMUP

Revista

Título: Journal of Biological Chemistry

Vol. 281

Páginas: 34888-34896

ISSN: 0021-9258

Editora: Elsevier

Indexação

ISI Web of Knowledge - 80 Citações

Scopus - 82 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Outras ciências médicas

Outras Informações

ID Authenticus: P-004-G21

DOI: 10.1074/jbc.m607067200

Abstract (EN): Helicobacter pylori interacts with gastric epithelial cells, activating signaling pathways important for carcinogenesis. In this study we examined the role of H. pylori on cell invasion and the molecular mechanisms underlying this process. The relevance of H. pylori cag pathogenicity island-encoded type IV secretion system (T4SS), CagA, and VacA for cell invasion was also investigated. We found that H. pylori induces AGS cell invasion in collagen type I and in Matrigel invasion assays. H. pylori-induced cell invasion requires the direct contact between bacteria and cancer cells. H. pylori-mediated cell invasion was dependent on the activation of the c-Met receptor and on increased MMP-2 and MMP-9 activity. The abrogation of the c-Met receptor using the specific NK4 inhibitor or the silencing of c-Met expression with small interference RNA suppressed both cell invasion and MMP activity. Studies with different H. pylori strains revealed that cell invasion, c-Met tyrosine phosphorylation, and increased MMP-2 and MMP-9 activity were all dependent on the presence of a functional bacterial T4SS, but not on VacA cytotoxicity. Our findings demonstrate that H. pylori strains with a functional T4SS stimulate gastric epithelial cell invasion through a c-Met-dependent signaling pathway that comprises an increase in MMP-2 and MMP-9 activity.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9