ACTG1 Inhibits PI3K/Akt Signaling Pathway to Promote Apoptosis in Gastric Cancer Cells Through Modulating Phosphatidylinositol3-Kinase Regulatory Subunits

Abstract

Gastric Cancer (GC) remains a leading cause of cancer-related mortality, with the PI3K/Akt pathway critically involved in its pathogenesis. This study identifies ACTG1 as a novel regulator of PI3K/Akt signaling, demonstrating its role in inducing caspase-dependent apoptosis. Through gain- and lossof-function experiments in SGC-7901 and HGC-27 cells, we show that ACTG1 overexpression reduces p-PI3K (Tyr458) by 62% and p-Akt (Ser473) by 58%, while increasing apoptotic cell populations by 2.8-3.2-fold. Clinically, ACTG1 expression negatively correlates with p-Akt levels in GC tissues (n=80, r=-0.41, p<0.01). These findings establish ACTG1 as a potential therapeutic target for PI3K/Akt-driven gastric cancer.