Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival.

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

SUBMITTER: Varghese RT 

PROVIDER: S-EPMC6134061 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature