Enhanced ITGA3 expression induced by helicobacter pylori infection facilitates gastric cancer progression via NF-κB and Smad4.

Helicobacter pylori (H. pylori) infection is a key risk factor in the onset and progression of gastric cancer (GC). The integrin subunit alpha 3 (ITGA3) is frequently upregulated in various malignancies and may influence cell proliferation and metastasis under specific conditions. However, the mechanisms that govern ITGA3 activation and its role in the inflammation-driven transformation of GC remain poorly understood. This study explores the impact of ITGA3 in response to H. pylori infection and its involvement in gastric tumorigenesis. Elevated ITGA3 expression was observed in gastric tissues and in GC cells exposed to H. pylori, and was associated with enhanced malignant phenotypes in vitro and increased tumor growth in vivo. Mechanistically, ITGA3 appears to promote GC progression, at least in part, through activation of the NF-κB/mTOR signaling axis and enhancement of TGF-β-related signaling, thereby contributing to tumor proliferation, epithelial-mesenchymal transition (EMT), and migration. Additionally, H. pylori infection led to an increase in p-STAT3 expression, which transcriptionally upregulates ITGA3, thereby further enhancing its pro-tumorigenic effects. This study suggests a previously underappreciated role for ITGA3 in H. pylori-associated GC. H. pylori infection induces p-STAT3 activation, driving ITGA3 expression at the transcriptional level. In turn, ITGA3 promotes GC progression by concurrently activating the NF-κB/mTOR and TGF-β signaling pathways, facilitating tumor cell proliferation, EMT, and migration, and thereby accelerating the malignancy of GC. These findings suggest that the ITGA3/NF-κB/mTOR/TGF-β axis may represent a potential therapeutic target for H. pylori-positive GC.