Effect of T-cadherin on the AKT/mTOR signaling pathway, gastric cancer cell cycle, migration and invasion, and its association with patient survival rate.

Abstract

Gastric cancer (GC) is among the most common types of human cancer and is associated with recurrence and metastasis, despite comprehensive surgical and medical treatment. Previous studies observed downregulation of T-cadherin expression in GC tissues, suggesting that this protein may act as an oncosuppressor. The current study investigated the activity of T-cadherin in GC tissues. In a follow-up study of 81 patients with GC, a Kaplan-Meier analysis of overall survival revealed a strong association of T-cadherin overexpression with increased overall survival (P<0.01). Furthermore, stable T-cadherin-overexpressing cell lines were established from HGC-27 cells via transfection of a pcDNA3.1-T-cadherin plasmid and in vitro growth and cell cycle of these cells were measured using MTT and flow cytometry assays, respectively. MTT assays revealed that proliferation of engineered T-cadherin-overexpressing cells was significantly inhibited and flow cytometry demonstrated that T-cadherin overexpression in HGC-27 cells induced cell cycle arrest in the G0/G1 phase. Transwell assays demonstrated that T-cadherin-overexpressing HGC-27 cells exhibited reduced invasiveness and metastatic potential. Phosphorylated (p)-protein kinase B (AKT) and p-mammalian target of rapamycin (mTOR) protein levels were reduced in T-cadherin overexpressing HGC-27 cells, suggesting that the AKT/mTOR signaling pathway was involved in the gastric tumor inhibitory effect of T-cadherin. Administration of AKT-activator, insulin-like growth factor-1, to T-cadherin-overexpressing HGC-27 cells significantly affected the proliferation phenotype. In conclusion, the current study provided clinical evidence and revealed a potential mechanism supporting that T-cadherin inhibits gastric tumorigenesis through inhibition of the AKT/mTOR signaling pathway.