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Activation of Laminin γ2 by Helicobacter pylori Promotes Invasion and Survival of Gastric Cancer Cells With E-Cadherin Defects.
Ferreira, Rui M; Figueiredo, Joana; Pinto-Ribeiro, Ines; Gullo, Irene; Sgouras, Dionyssios N; Carreto, Laura; Castro, Patricia; Santos, Manuel A; Carneiro, Fatima; Seruca, Raquel; Figueiredo, Ceu.
Afiliação
  • Ferreira RM; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
  • Figueiredo J; Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
  • Pinto-Ribeiro I; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
  • Gullo I; Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
  • Sgouras DN; Department of Pathology, Faculty of Medicine, University of Porto, Porto, Portugal.
  • Carreto L; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
  • Castro P; Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
  • Santos MA; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
  • Carneiro F; Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
  • Seruca R; Department of Pathology, Faculty of Medicine, University of Porto, Porto, Portugal.
  • Figueiredo C; Department of Pathology, Centro Hospitalar Universitário São João, Porto, Portugal.
J Infect Dis ; 226(12): 2226-2237, 2022 12 13.
Article em En | MEDLINE | ID: mdl-36173814
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 γ2, 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 γ2 and E-cadherin expression patterns were evaluated in gastric cancer cases. RESULTS: Laminin γ2 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 γ2 overexpression is dependent on the bacterial type IV secretion system and on the CagA. Functionally, laminin γ2 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 γ2 and its downstream effectors as potential therapeutic targets, and the value of H. pylori eradication to delay gastric cancer onset and progression.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Helicobacter pylori / Infecções por Helicobacter Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Helicobacter pylori / Infecções por Helicobacter Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article