SKA3 promotes glioblastoma proliferation and invasion by enhancing the activation of Wnt/β-catenin signaling via modulation of the Akt/GSK-3β axis.

Spindle and kinetochore-related complex subunit 3 (SKA3) is a key modulator of the progression of multiple tumor types. However, the involvement of SKA3 in glioblastoma (GBM) has not been well studied. The current study aimed to explore the role of SKA3 expression and the potential function of the protein in GBM. Our data showed that SKA3 expression was significantly up-regulated in GBM. Functional assays demonstrated that the knockdown of SKA3 impeded the proliferation, colony formation and invasion of GBM cells, while SKA3 overexpression produced the opposite effects. Further investigation revealed that SKA3 overexpression enhanced the activation of Wnt/β-catenin signaling, which was associated with the enhanced phosphorylation of Akt and glycogen synthase kinase-3β (GSK-3β). Notably, the inhibition of Akt markedly abrogated the SKA3 overexpression-induced promotion of Wnt/β-catenin signaling in GBM cells. Further, the inhibition of Wnt/β-catenin signaling markedly abrogated the SKA3 overexpression-induced promotion of tumor growth. In addition, the knockdown of SKA3 significantly retarded tumor formation and GBM progression in vivo. In summary, these data demonstrate that SKA3 exerts promotes tumor growth in GBM by enhancing the activation of Wnt/β-catenin signaling via modulation of the Akt/GSK-3β axis. This work highlights the pivotal role of SKA3/Akt/GSK-3β/Wnt/β-catenin signaling in the progression of GBM and suggests that SKA3 is an attractive therapeutic target with potential to be used to treat GBM.