CSNK1D is associated with stemness and invasiveness in glioblastoma

Abstract

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor. It has a poor 5-year survival rate, a high recurrence rate, and few therapeutic options. Exploring the molecular processes underlying the formation and progression of GBM, as well as identifying novel therapeutic targets, is critical for improving GBM therapy and prognosis.

Methods: We extracted primary GSCs (glioblastoma stem cells) from patient-derived samples. Different levels of CSNK1D were evaluated through immunohistochemistry, western blot and real-time PCR assays. A Transwell assay was used to detect invasive ability of cell lines. Tumorsphere formation assay was performed to detect cancer stemness properties. Orthotopic xenograft models were used to evaluate the effect of CSNK1D on GSC tumorigenesis.

Results: We found the expression levels of CSNK1D was elevated in GBM tissues compared with normal brain. CSNK1D expression had an increased tendency among WHO grades (G2-G4), and was higher in IDH wildtype group than in mutation group. The prognosis of the CSNK1D high expression group was significantly worse than that of the low expression group. Cox multivariate analysis showed that CSNK1D was also an independent prognostic factor in GBM patients. In primary GBM cells, we observed increased levels of CSNK1D in GSCs compared to non-stem tumor cells (NSTCs). In addition, the change of stemness markers expression and proliferation of GSCs were in coordinate with CSNK1D overexpression or knockdown. Furthermore, CSNK1D could affect the epithelial-mesenchymal transition (EMT) markers and MMPs expression in GSCs. Finally, disruption of CSNK1D expression impairs GSC survival and GBM tumor propagation in orthotopic xenograft models.

Conclusion: Our results suggest that CSNK1D correlated with GBM prognosis and might influence the stemness and invasiveness of GSCs, which represented a potential therapeutic target in GBM patients.

Keywords: GSCs; Glioblastoma; Invasiveness; Prognosis; Stemness.