Plexin-domain containing 2 promotes invasion and metastasis of gastric cancer by regulating filopodia formation

Objective To investigate the role of plexin-domain containing 2 (PLXDC2) in regulating the invasion and metastasis of gastric cancer (GC) and explore its mechanism. Methods The data of GC cases were collected from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) database, and the relationship between PLXDC2 expression and the clinicopathological parameters as well as the prognosis of GC patients were statistically analyzed. PLXDC2 knockdown and overexpression GC cell models were constructed respectively, then Matrigel-transwell invasion assay and mouse peritoneal metastasis model were performed to evaluate the effect of PLXDC2 on the invasion and metastasis of GC cells. Western blotting and immunofluorescence assay were also adopted to investigate the potential mechanism of PLXDC2 in GC. Results PLXDC2 was highly expressed in GC tissues (P < 0.05), and its expression level was positively correlated with neoplasm histological grade (P < 0.01), TNM stage (P < 0.05) and T stage (P < 0.05), while negatively with the prognosis of patients (P < 0.05). Cox regression analysis identified PLXDC2 as an independent risk factor for prognosis (P < 0.05). Silencing PLXDC2 significantly inhibited the invasion ability of GC cells in vitro (P < 0.01) and metastasis in vivo (P < 0.01), whereas overexpression of PLXDC2 obtained the opposite results. Moreover, the changes of PLXDC2 level correspondingly affected the expression of Cdc42 and the formation of filopodia in GC cells. Conclusion PLXDC2 promotes the invasion and metastasis of GC cells by regulating the formation of filopodia, and may act as a potential prognostic biomarker and therapeutic target for GC.