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

2 Citations (Scopus)

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

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Casein Kinase Iepsilon
Glioblastoma
Cell Survival
Catenins
Stem Cells
Growth
Casein Kinase I

All Science Journal Classification (ASJC) codes

  • General

Cite this

Varghese, R. T., Young, S., Pham, L., Liang, Y., Pridham, K. J., Guo, S., ... 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
Varghese, Robin T. ; Young, Sarah ; Pham, Lily ; Liang, Yanping ; Pridham, Kevin J. ; Guo, Sujuan ; Murphy, Susan ; Kelly, Deborah F. ; Sheng, Zhi. / Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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Varghese, RT, Young, S, Pham, L, Liang, Y, Pridham, KJ, Guo, S, Murphy, S, Kelly, DF & Sheng, Z 2018, 'Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival', Scientific reports, vol. 8, no. 1, 13621. https://doi.org/10.1038/s41598-018-31864-x

Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival. / Varghese, Robin T.; Young, Sarah; Pham, Lily; Liang, Yanping; Pridham, Kevin J.; Guo, Sujuan; Murphy, Susan; Kelly, Deborah F.; Sheng, Zhi.

In: Scientific reports, Vol. 8, No. 1, 13621, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Varghese, Robin T.

AU - Young, Sarah

AU - Pham, Lily

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AU - Guo, Sujuan

AU - Murphy, Susan

AU - Kelly, Deborah F.

AU - Sheng, Zhi

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Varghese RT, Young S, Pham L, Liang Y, Pridham KJ, Guo S et al. Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival. Scientific reports. 2018 Dec 1;8(1). 13621. https://doi.org/10.1038/s41598-018-31864-x