Background
Spindle and kinetochore-related complex subunit 3 (SKA3), a member of the SKA family of proteins, is associated with the progression of multiple cancers. However, the role of SKA3 in gastric cancer has not been studied.
Conclusion
Our results indicate that the SKA3-DUSP2-ERK1/2 axis is involved in the regulation of gastric cancer progression, and SKA3 is a potential therapeutic target for gastric cancer.
Methods
The expression levels of SKA3 and dual-specificity phosphatase 2 (DUSP2) proteins were detected by immunohistochemistry. The effects of SKA3 and DUSP2 on the proliferation, migration, invasion, adhesion, and epithelial-mesenchymal transition of gastric cancer were studied in vitro and in vivo.
Results
Immunohistochemical analysis of 164 cases of gastric cancer revealed that high expression of SKA3 was negatively correlated with DUSP2 expression and related to N stage, peritoneal metastasis, and poor prognosis. In vitro studies showed that silencing SKA3 expression inhibited the proliferation, migration, invasion, adhesion and epithelial-mesenchymal transition of gastric cancer. In vivo experiments showed that silencing SKA3 inhibited tumor growth and peritoneal metastasis. Mechanistically, SKA3 negative regulates the tumor suppressor DUSP2 and activates the MAPK/ERK pathway to promote gastric cancer.