Constitutive activation of casein kinase 2 in glioblastomas: Absence of class restriction and broad therapeutic potential

  • Authors:
    • Nadege Dubois
    • Marie Willems
    • Minh-Tuan Nguyen-Khac
    • Jerome Kroonen
    • Nicolas Goffart
    • Manuel Deprez
    • Vincent Bours
    • Pierre A. Robe
  • View Affiliations

  • Published online on: April 18, 2016     https://doi.org/10.3892/ijo.2016.3490
  • Pages: 2445-2452
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Casein kinase II contributes to the growth and survival of malignant gliomas and attracts increasing attention as a therapeutic target in these tumors. Several reports have suggested that this strategy might be most relevant for specific subgroups of patients, namely Verhaak's classical and TP53 wild-type tumors. Using kinase assays and microarray genetic profiling in a series of 27 proprietary fresh frozen surgical glioma samples, we showed that constitutive CK2 kinase activation is not restricted to tumors that present increased copy numbers or mRNA expression of its catalytic or regulatory subunits, and can result from a functional activation by various cytokines from the glioma microenvironment. Using corresponding primary tumor and human astrocyte cell cultures as well as glioma cell lines, we confirmed that CK2 inhibition is selectively toxic to malignant glial tumors, without any restriction to tumor class or to TP53 status. We finally showed that while the contribution of CK2 to the constitutive NF-κB hyperactivation in malignant gliomas is at best moderate, a delayed activation of NF-κB may associate with the therapeutic resistance of glioma cells to CK2 inhibition.
View Figures
View References

Related Articles

Journal Cover

June-2016
Volume 48 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Dubois N, Willems M, Nguyen-Khac M, Kroonen J, Goffart N, Deprez M, Bours V and Robe PA: Constitutive activation of casein kinase 2 in glioblastomas: Absence of class restriction and broad therapeutic potential. Int J Oncol 48: 2445-2452, 2016
APA
Dubois, N., Willems, M., Nguyen-Khac, M., Kroonen, J., Goffart, N., Deprez, M. ... Robe, P.A. (2016). Constitutive activation of casein kinase 2 in glioblastomas: Absence of class restriction and broad therapeutic potential. International Journal of Oncology, 48, 2445-2452. https://doi.org/10.3892/ijo.2016.3490
MLA
Dubois, N., Willems, M., Nguyen-Khac, M., Kroonen, J., Goffart, N., Deprez, M., Bours, V., Robe, P. A."Constitutive activation of casein kinase 2 in glioblastomas: Absence of class restriction and broad therapeutic potential". International Journal of Oncology 48.6 (2016): 2445-2452.
Chicago
Dubois, N., Willems, M., Nguyen-Khac, M., Kroonen, J., Goffart, N., Deprez, M., Bours, V., Robe, P. A."Constitutive activation of casein kinase 2 in glioblastomas: Absence of class restriction and broad therapeutic potential". International Journal of Oncology 48, no. 6 (2016): 2445-2452. https://doi.org/10.3892/ijo.2016.3490