CKS2 promotes tumor progression and metastasis and is an independent predictor of poor prognosis in epithelial ovarian cancer.

Abstract

Accumulating evidence showed that dysregulation of cyclin-dependent kinases regulatory subunit 2 (CKS2) could contribute to tumor growth and metastasis of several tumors. However, its expression and function in epithelial ovarian cancer (EOC) have not been investigated. Here, we aimed to investigate the role of CKS2 in EOC. Real-time PCR and Western blotting were used to determine the mRNA and protein expression of CKS2 in EOC tissues and cell lines. Then, the associations of CKS2 expression with clinicopathological features and patient's overall survival were determined. Proliferation assay flow cytometric analysis and transwell assay were performed to detect the relation between CKS2 and malignant behaviors of EOC cells. We also evaluated the expression of related proteins of the Akt/mTOR pathway to determine the associated molecular mechanism. We found that CKS2 expression was significantly up-regulated in both EOC tissues and cell lines. Clinically, high expression of CKS2 was associated with advanced FIGO stage, histological grade and shorter overall survival of EOC patients. We also found that knockdown of CKS2 suppressed proliferation, invasion, and migration of EOC cells in vitro, and CKS2 could promote EMT progress by modulating EMT-related molecules. Finally, Western blot demonstrated that down-regulation of CKS2 suppressed the expression of p-Akt and p-mTOR. Our findings indicated that CKS2 might function as a tumor promoter by modulating Akt/mTOR pathway in EOC and could serve as a promising prognostic biomarker for EOC.