Nuclear Pore Complex 62 Promotes Metastasis of Gastric Cancer by Regulating Wnt/β-Catenin and TGF-β Signaling Pathways.

Abstract

Gastric cancer (GC) is the third leading cause of cancer-related deaths in the world. Tumor metastasis is considered one of the main factors for GC development. Nup62 is a member of the nuclear pore complex (NPC). It bridges the nuclear envelope, is important in nucleocytoplasmic exchange, and is associated with cancer. This study aimed to investigate the role of Nup62 in GC metastasis. The relationship between the expression level of Nup62 in GC and patient survival was evaluated using Kaplan-Meier analysis. Then Nup62 expression in GC tissues and matched normal gastric tissues was analyzed by immunohistochemistry and that in cell lines by Western blot analysis. Furthermore, clonogenic and Transwell migration assays were performed, and the expression of epithelial-mesenchymal transition (EMT) proteins was detected to determine the metastatic functional roles of Nup62 in GC. Compared with the adjacent normal tissues, Nup62 was found to be upregulated in GC tissues using software prediction and detecting clinical specimens and cell lines. Moreover, the downregulation of Nup62 suppressed colony formation and decreased the number of migrated cells. In contrast, Nup62 overexpression promoted colony formation and increased the number of migrated cells. Further functional studies showed that the abnormal expression of Nup62 influenced cell migration and EMT through wingless/β-catenin (Wnt/β-catenin) and transforming growth factor (TGF)-β signaling pathways. In summary, the findings indicate that Nup62 regulates cell migration by interfering with Wnt/β-catenin and TGF-β signaling pathways in GC.