Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival.
Sci Rep
; 8(1): 13621, 2018 09 11.
Article
in En
| MEDLINE
| ID: mdl-30206363
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 ß-catenin and induced apoptosis, which was further counteracted by knockdown of ß-catenin. The CK1ε inhibitor IC261, but not PF-4800567, activated ß-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 ß-catenin signaling, underscoring the importance of targeting CK1ε as an effective treatment for glioblastoma.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Glioblastoma
/
Casein Kinase I
/
Neoplasm Proteins
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Sci Rep
Year:
2018
Document type:
Article
Affiliation country: