Downregulation of EPHA2 Receptor Tyrosine Kinase by Helicobacter pylori in Gastric Epithelial Cells: Implications for Gastric Cancer Progression

Document Type : Research Articles

Authors

Sedighe Kohgard

Saber Zahri

Saeid Latifi Navid

Maryam Jahanvar

Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran

https://doi.org/10.22067/jcmr.2025.92344.1106

Abstract

Helicobacter pylori is a Gram-negative bacterium that persistently colonizes the gastric mucosa, leading to various gastrointestinal disorders, including gastritis, peptic ulcers, and gastric cancer. Chronic H. pylori infection triggers inflammatory responses and modulates host signaling pathways, particularly receptor tyrosine kinases (RTKs), which regulate essential cellular processes such as adhesion, migration, proliferation, and survival. Among these, EphA2 is a key RTK involved in epithelial cell signaling and maintaining structural integrity, while E-cadherin plays a critical role in cell-cell adhesion and tumor suppression. Disruptions in these signaling molecules can contribute to gastric epithelial dysfunction and cancer progression. This study aimed to evaluate the effects of an Iranian H. pylori vacA d1/-i1 strain on the expression of EPHA2 and E-cadherin in AGS gastric epithelial cells. Following co-culture with H. pylori, total RNA was extracted, and quantitative real-time PCR (qRT-PCR) was performed to analyze gene expression levels. Hematoxylin and eosin (H&E) staining was used to assess morphological changes, revealing structural alterations indicative of cellular stress and epithelial disruption after H. pylori infection. Gene expression analysis demonstrated a significant downregulation of EPHA2 in H. pylori-infected cells compared to controls (p < 0.0001), suggesting bacterial interference with EPHA2-mediated signaling pathways. In contrast, no significant change in E-cadherin expression was observed, indicating that H. pylori may not strongly impact cell adhesion under these conditions. The selective suppression of EPHA2, along with observed morphological changes, suggests a novel mechanism by which H. pylori contribute to gastric epithelial dysfunction, potentially promoting tumorigenesis. Further research is needed to elucidate the molecular pathways involved and their implications for gastric disease pathogenesis and targeted therapeutic strategies.

Keywords

Keywords: Helicobacter pylori

EPHA2

E-cadherin

receptor tyrosine kinases

gastric epithelial cells

gastric cancer

hematoxylin and eosin staining

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