Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival

Robin T. Varghese, Sarah Young, Lily Pham, Yanping Liang, Kevin J. Pridham, Sujuan Guo, Susan Murphy, Deborah F. Kelly, Zhi Sheng

Research output: Contribution to journalArticle

8 Scopus citations

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 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.

Original languageEnglish (US)
Article number13621
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

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    Varghese, R. T., Young, S., Pham, L., Liang, Y., Pridham, K. J., Guo, S., Murphy, S., Kelly, D. F., & Sheng, Z. (2018). Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival. Scientific reports, 8(1), [13621]. https://doi.org/10.1038/s41598-018-31864-x