Activation of laminin γ2 by helicobacter pylori promotes invasion and survival of gastric cancer cells with e-cadherin defects

Rui M. Ferreira, Joana Figueiredo, Ines Pinto-Ribeiro, Irene Gullo, Dionyssios N. Sgouras, Laura Carreto, Patricia Castro, Manuel A. Santos, Fatima Carneiro, Raquel Seruca, Ceu Figueiredo

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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 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.
Original languageEnglish
Pages (from-to)2226-2237
Number of pages12
JournalThe Journal of infectious diseases
Volume226
Issue number12
DOIs
Publication statusPublished - 15 Dec 2022
Externally publishedYes

Keywords

  • CagA
  • E-cadherin
  • Gastric carcinoma
  • Helicobacter pylori
  • Laminin γ2

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