Portal de investigação
Activation of Laminin ?2 by Helicobacter pylori Promotes Invasion and Survival of Gastric Cancer Cells With E-Cadherin Defects
Autores da FMUP
Participantes de fora da FMUP
- Ferreira, RM
- Pinto-Ribeiro, I
- Sgouras, DN
- Carreto, L
- Castro, P
- Santos, MA
- Seruca, R
Unidades de investigação
Abstract
Background. Helicobacter pylori infection induces cellular phenotypes relevant for cancer progression, namely cell motility and invasion. We hypothesized that the extracellular matrix (ECM) could be involved in these deleterious effects. Methods. Microarrays were used to uncover ECM interactors in cells infected with H. pylori. LAMC2, encoding laminin gamma 2, was selected as a candidate gene and its expression was assessed in vitro and in vivo. The role of LAMC2 was investigated by small interference RNA (siRNA) combined with a set of functional assays. Laminin gamma 2 and E-cadherin expression patterns were evaluated in gastric cancer cases. Results. Laminin gamma 2 was found significantly overexpressed in gastric cancer cells infected with H. pylori. This finding was validated in vitro by infection with clinical isolates and in vivo by using gastric biopsies of infected and noninfected individuals. We showed that laminin gamma 2 overexpression is dependent on the bacterial type IV secretion system and on the CagA. Functionally, laminin gamma 2 promotes cell invasion and resistance to apoptosis, through modulation of Src, JNK, and AKT activity. These effects were abrogated in cells with functional E-cadherin. Conclusions. These data highlight laminin gamma 2 and its downstream effectors as potential therapeutic targets, and the value of H. pylori eradication to delay gastric cancer onset and progression.
Dados da publicação
- ISSN/ISSNe:
- 0022-1899, 1537-6613
- Tipo:
- Article
- Páginas:
- 2226-2237
- Link para outro recurso:
- www.scopus.com
Journal of Infectious Diseases Oxford University Press
Citações Recebidas na Web of Science: 2
Citações Recebidas na Scopus: 5
Documentos
- Não há documentos
Filiações
Keywords
- gastric carcinoma; cagA; e-cadherin; Helicobacter pylori; laminin gamma 2
Financiamento
Proyectos asociados
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Estudo Clínico Académico (Helicobacter) . 2019
The role of hepatocyte apoptosis markers in predicting the histological and serological activity in steatohepatitis
Investigador Principal: Maria de Fátima Machado Henriques Carneiro
Estudo Clínico Académico . 2021
Immune checkpoint inhibitors for the treatment of gastric cancer
Investigador Principal: Maria do Céu Fontes Herdeiro Figueiredo
Estudo Clínico Académico . 2021
Evaluation of the use of Helicobacter pylori genotypes and gastric microbiota markers to identify individuals at high risk of gastric carcinoma
Investigador Principal: Maria do Céu Fontes Herdeiro Figueiredo
Estudo Clínico Académico . 2021
Gastric Cancer Morphological, Immunophenotypic and molecular heterogeneity
Investigador Principal: Maria de Fátima Machado Henriques Carneiro
Estudo Clínico Académico . 2020
Citar a publicação
Ferreira RM,Figueiredo J,Pinto I,Gullo I,Sgouras DN,Carreto L,Castro P,Santos MA,Carneiro F,Seruca R,Figueiredo C. Activation of Laminin ?2 by <i>Helicobacter pylori</i> Promotes Invasion and Survival of Gastric Cancer Cells With E-Cadherin Defects. J. Infect. Dis. 2022. 226. (12):p. 2226-2237. IF:6,400. (1).
