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 ε (CK1ε， also known as CSNK1E) as a potential survival factor in glioblastoma. However， how CK1ε controls cell survival remains elusive and whether targeting CK1ε is a possible treatment for glioblastoma requires further investigation. Here we report that CK1ε was expressed at the highest level among six CK1 isoforms in glioblastoma and enriched in high-grade glioma， but not glia cells. Depletion of CK1ε remarkably inhibited the growth of glioblastoma cells and suppressed self-renewal of glioblastoma stem cells， while having limited effect on astrocytes. CK1ε deprivation activated β-catenin and induced apoptosis， which was further counteracted by knockdown of β-catenin. The CK1ε inhibitor IC261， but not PF-4800567， activated β-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 CK1ε regulates the survival of glioblastoma cells and glioblastoma stem cells through β-catenin signaling， underscoring the importance of targeting CK1ε as an effective treatment for glioblastoma.