Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival

Glioblastoma is the most common malignant brain cancer with a dismal prognosis. The difficulty in treating glioblastoma is largely attributed to the lack of effective therapeutic targets. In our previous work, we identified casein kinase 1 epsilon (CK1 epsilon, also known as CSNK1E) as a potential survival factor in glioblastoma. However, how CK1 epsilon controls cell survival remains elusive and whether targeting CK1 epsilon is a possible treatment for glioblastoma requires further investigation. Here we report that CK1 epsilon was expressed at the highest level among six CK1 isoforms in glioblastoma and enriched in high-grade glioma, but not glia cells. Depletion of CK1 epsilon remarkably inhibited the growth of glioblastoma cells and suppressed self-renewal of glioblastoma stem cells, while having limited effect on astrocytes. CK1 epsilon deprivation activated beta-catenin and induced apoptosis, which was further counteracted by knockdown of beta-catenin. The CK1 epsilon inhibitor IC261, but not PF-4800567, activated beta-catenin and blocked the growth of glioblastoma cells and glioblastoma stem cells. Congruently, IC261 elicited a robust growth inhibition of human glioblastoma xenografts in mice. Together, our results demonstrate that CK1 epsilon regulates the survival of glioblastoma cells and glioblastoma stem cells through beta-catenin signaling, underscoring the importance of targeting CK1 epsilon as an effective treatment for glioblastoma.