Activation of Laminin gamma 2 by Helicobacter pylori Promotes Invasion and Survival of Gastric Cancer Cells With E-Cadherin Defects

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Ferreira, RM (Author) Other; Figueiredo, J (Author) Other; Pinto Ribeiro, I (Author) Other; Gullo, I (Author) Other; Sgouras, DN (Author) Other; Carreto, L (Author) Other; Castro, P (Author) Other; Santos, MA (Author) Other; Carneiro F (Author) FMUP; Seruca, R (Author) Other; Figueiredo C (Author) FMUP

Journal

Title: Journal of Infectious Diseases

Vol. 226

Pages: 2226-2237

ISSN: 0022-1899

Publisher: Oxford University Press

Indexing

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Other information

Authenticus ID: P-00X-83S

DOI: 10.1093/infdis/jiac397

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12