CKS2 promotes the malignant phenotypes of bladder cancer cells via PI3K/AKT signaling pathway activation.

Cyclin-dependent kinase subunit 2 (CKS2) has been implicated in various malignancies. This study investigates the mechanism by which CKS2 contributes to bladder cancer (BC) progression. Abnormally expressed genes were identified by differential analysis of tumor and normal tissues using Gene Expression Omnibus datasets. Subsequently, functional assays - including cell proliferation, Transwell migration, colony formation, wound healing, flow cytometry, and enzyme-linked immunosorbent assays - were performed to provide cellular evidence supporting the oncogenic function of CKS2 in BC. The results demonstrated significantly elevated CKS2 expression in BC cells than in normal urothelial cells. CKS2 overexpression promoted cell proliferation, cell migration and invasion. Mechanistically, CKS2 overexpression caused a marked reduction in PTEN protein levels, thereby inhibiting PIP3 degradation and indirectly activating the PI3K/AKT signaling pathway. Furthermore, CKS2 promoted phosphorylation and degradation of p27 Kip1 (Thr187), consequently contributing to cell cycle deregulation and further enhancing PI3K/AKT pathway activity. In contrast, CKS2 knockdown produced the opposite effects. Notably, treatment with the PI3K inhibitor LY294002 effectively reversed CKS2-induced BC cell proliferation and metastasis. In conclusion, CKS2 promoted the malignant phenotypes of BC cells by enhancing PI3K/AKT pathway activity through dual mechanisms involving PTEN downregulation and p27 Kip1-mediated cell cycle dysregulation.