Abstract
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. 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. 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.
Highlights
Gastric cancer (GC) has a high morbidity and mortality rate worldwide
Spindle and kinetochore-related complex subunit 3 (SKA3) is highly expressed in GC, negatively correlates with Dual-specific phosphatase 2 (DUSP2) expression and is associated with poor prognosis in GC
We performed immunohistochemistry of 164 GC tumor samples and found that SKA3 and DUSP2 were mainly expressed in the cytoplasm and nucleus (Figure 1G)
Summary
Gastric cancer (GC) has a high morbidity and mortality rate worldwide. GC patients can benefit from surgery and chemoradiotherapy, the 5 years survival rate is only 40% (Noh et al, 2014; Bray et al, 2018). The poor survival rate of patients with GC after surgery is mostly from metastasis and recurrence after surgery. Recent studies showed that SKA3 plays a cancer-promoting role, by affecting the proliferation of tumor cells through regulating cell cycle checkpoints, and by participating in a variety of cell biological functions to affect the occurrence and development of tumors (Jiao et al, 2013; Pesson et al, 2014; Lee et al, 2015; Hou et al, 2019). The role of SKA3 in gastric cancer has not been studied
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