Role of ADP ribosylation factor guanylate kinase 1 in the malignant biological behavior of gastric cancer.

Aim: This study aims to investigate the influence of (ADP ribosylation factor guanylate kinase 1) on the malignant behavior of gastric cancer (GC) cells and to elucidate the potential molecular mechanisms involved in cancer development and progression.

Methods: We assessed the impact of overexpression and knockdown on GC cell malignancy using CCK8, colony formation, flow cytometry (Annexin V/propidium iodide), Transwell migration, invasion, and scratch assays. Western blot analysis was used to assess the effects of on angiogenesis, matrix metalloproteinases (MMPs), apoptotic proteins, epithelial-mesenchymal transition (EMT)-related proteins, as well as AKT and -AKT. The influence of knockdown was also evaluated in nude mice bearing BGC823 cell-derived tumors.

Results: Our findings revealed that was significantly overexpressed in GC cells, enhancing their proliferation, invasion, and migration, while reducing apoptosis. Conversely, knockdown reversed these effects, markedly increasing the expression of cleaved-caspase 3 (Casp3), PARP, and the epithelial marker E-cadherin, and significantly decreasing MMP2, MMP9, VEGFA, and mesenchymal markers such as N-cadherin and vimentin. Additionally, it reduced AKT, and -AKT levels ( < 0.01). Tumor growth in nude mice was suppressed following knockdown.

Conclusion: The overexpression of significantly promotes malignant behaviors in GC cells, whereas its knockdown diminishes these effects. This modulation is potentially through the downregulation of VEGFA, leading to reduced angiogenesis, Cleaved-Casp3 and Cleaved-PARP overexpression, and a decrease in MMPs, EMT, AKT, and -AKT activity.