Girdin acts as an oncogene in gastric cancer by regulating AKT/GSK3β/β-catenin signaling

ThE present work focused on exploring Girdin expression within gastric cancer (GC), examining the effect of Girdin on the cell phenotype of GC, and clarifying the underlying mechanisms. Girdin expression in GC samples was identified by immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) assays. Girdin-targeting siRNAs were transfected into GC cells; later, we examined GC cell proliferation, migration, invasion, and apoptosis, respectively. Additionally, the protein expression was examined through Western blotting assay. Moreover, the tumor implantation experiment was conducted for examining Girdin knockdown in vivo. The results showed that Girdin expression elevated within GC samples, which was associated with the dismal prognostic outcome. Girdin knockdown suppressed GC cell proliferation, migration, and invasion, and enhanced apoptosis and cell cycle arrest. Girdin promoted the phosphorylation of AKT, GSK3 beta, and beta-catenin. Moreover, Girdin inhibited the phosphorylation of beta-catenin. Girdin suppressed cell apoptosis and stimulated cell migration and invasion, while AKT inhibitor (MK2206) treatment reversed the effect of Girdin overexpression, and GSK3 beta inhibitor (CHIR99021) treatment enhanced the effect of Girdin overexpression on GC cells. Besides, Girdin delayed tumor growth in vivo. In conclusion, Girdin was abnormally expressed in GC samples, which promoted the development of GC by regulating AKT/GSK3 beta/beta-catenin signaling.

Automated summary

The present study investigated the expression and function of Girdin in gastric cancer (GC). Girdin expression was found to be elevated in GC samples and correlated with poor prognosis. Knockdown of Girdin inhibited GC cell proliferation, migration, and invasion, while promoting apoptosis and cell cycle arrest. Girdin was found to regulate AKT/GSK3 beta/beta-catenin signaling and its overexpression could be reversed by AKT inhibitor treatment and enhanced by GSK3 beta inhibitor treatment. In vivo experiments showed that Girdin delayed tumor growth. These findings suggest that Girdin plays a role in promoting GC development.