Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival
| dc.contributor.author | Varghese, Robin T. | en |
| dc.contributor.author | Young, Sarah | en |
| dc.contributor.author | Pham, Lily | en |
| dc.contributor.author | Liang, Yanping | en |
| dc.contributor.author | Pridham, Kevin J. | en |
| dc.contributor.author | Guo, Sujuan | en |
| dc.contributor.author | Murphy, Susan F. | en |
| dc.contributor.author | Kelly, Deborah F. | en |
| dc.contributor.author | Sheng, Zhi | en |
| dc.date.accessioned | 2018-09-12T13:05:49Z | en |
| dc.date.available | 2018-09-12T13:05:49Z | en |
| dc.date.issued | 2018-09-11 | en |
| dc.description.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. | en |
| dc.description.sponsorship | Virginia Tech Carilion Research Institute | en |
| dc.description.sponsorship | Virginia Tech Carilion School of Medicine | en |
| dc.description.sponsorship | American Brain Tumor Association | en |
| dc.identifier.doi | https://doi.org/10.1038/s41598-018-31864-x | en |
| dc.identifier.issue | 1 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/85004 | en |
| dc.identifier.volume | 8 | en |
| dc.language.iso | en_US | en |
| dc.publisher | Nature | en |
| dc.rights | Creative Commons Attribution 3.0 United States | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | en |
| dc.title | Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival | en |
| dc.title.serial | Scientific Reports | en |
| dc.type | Article - Refereed | en |