Faciogenital dysplasia 5 confers the cancer stem cell-like traits of gastric cancer cells through enhancing Sox2 protein stability.

The promoting roles of faciogenital dysplasia 5 (FGD5) in tumor progression have been identified in various tumors, however, its roles in gastric cancer progression are still confusing. Currently, it was found that FGD5 was highly expressed in gastric cancer tissues and negatively correlated with different types of survival of gastric cancer patients via online dataset analysis. In vitro analysis of different types of gastric cancer cell lines and normal gastric epithelial cells obtained a consistent result. Then FGD5 was knocked down in gastric cancer cell lines through two independent siRNAs against FGD5 and it was identified that FGD5 knockdown suppressed the cancer stem cell (CSC)-like traits of gastric cancer cells through analyzing the expression of CSC markers, ALDH1 activity and spheroid-formation ability. Further mechanistic studies revealed that FGD5 interacted with Sox2 protein, a critical regulator of CSC progression, enhanced Sox2 protein stability and decreased its ubquitination. Additionally, FGD5 supported the CSC-like traits dependent on Sox2 expression. Taken together, this work identified a novel FGD5/Sox2 axis responsible for the CSC-like traits of gastric cancer cells.