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.

中文翻译：

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面部生殖器发育不良5通过增强Sox2蛋白稳定性赋予胃癌细胞的癌症干细胞样特征

面部生殖器发育不良5（FGD5）在肿瘤进展中的促进作用已在各种肿瘤中得到证实，但其在胃癌进展中的作用仍然令人困惑。目前，通过在线数据集分析发现，FGD5在胃癌组织中高表达，与不同类型胃癌患者的生存期呈负相关。不同类型胃癌细胞系和正常胃上皮细胞的体外分析得到了一致的结果。然后通过两个独立的针对 FGD5 的 siRNA 在胃癌细胞系中敲低 FGD5，通过分析 CSC 标志物的表达、ALDH1 活性和球状体，确定 FGD5 敲低抑制了胃癌细胞的癌症干细胞 (CSC) 样特征- 形成能力。进一步的机制研究表明，FGD5 与 Sox2 蛋白相互作用，Sox2 蛋白是 CSC 进展的关键调节因子，增强了 Sox2 蛋白的稳定性并降低了其泛素化。此外，FGD5 支持依赖于 Sox2 表达的 CSC 样特征。总之，这项工作确定了一个新的 FGD5/Sox2 轴，负责胃癌细胞的 CSC 样特征。