SLC30A2-Mediated Zinc Metabolism Modulates Gastric Cancer Progression via the Wnt/β-Catenin Signaling Pathway.

Abstract

Gastric cancer (GC) is a significant global health burden with limited treatment options. The purpose of this study was to investigate the role of SLC30A2, a zinc transporter, in GC development and its capacity as a target for therapy. A comprehensive analysis of GC datasets (GSE54129 and stomach adenocarcinoma (STAD) from The Cancer Genome Atlas (TCGA)) was conducted using bioinformatics tools to examine differential gene expression, focusing on SLC30A2. Functional assays, including Cell counting kit-8 (CCK-8) and transwell assays, were carried out on GC cell lines to determine the impact of SLC30A2 knockdown on cell behavior. Flow cytometry was utilized to quantitatively observe cell apoptosis and cell cycle progression. The impact of zinc sulfate (ZnSO4) on GC cells was evaluated by detecting apoptosis markers, Wnt/β-catenin signaling pathway activity, and oxidative stress biomarkers, focusing on the regulatory effect of SLC30A2 overexpression. Our analysis revealed significant upregulation of SLC30A2 in GC samples compared to normal samples, and high SLC30A2 expression was linked to poor prognosis. SLC30A2 knockdown repressed proliferation, invasion, and migration of GC cells, induced apoptosis, as well as arrested the cell cycle. Additionally, ZnSO4 treatment induced cytotoxicity and oxidative stress in GC cells, while SLC30A2 overexpression rescued ZnSO4-induced, migration, invasion, and proliferation. Moreover, ZnSO4 had been shown to bolster apoptosis and trigger the Wnt/β-catenin signaling pathway, effects which were mitigated by the overexpression of SLC30A2. Our results implied that SLC30A2 was essential for GC progression by modulating zinc homeostasis and cellular processes. Targeting SLC30A2 or zinc signaling may represent a potential therapeutic approach for GC treatment.