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

Nadege Dubois, Marie Willems, Minh-Tuan Nguyen-Khac, Jerome Kroonen, Nicolas Goffart, Manuel Deprez, Vincent Bours, Pierre A Robe

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)2445-52
Number of pages8
JournalInternational Journal of Oncology
Issue number6
Publication statusPublished - Jun 2016
Externally publishedYes


  • Apigenin/pharmacology
  • Brain Neoplasms/enzymology
  • Casein Kinase II/antagonists & inhibitors
  • Cell Line, Tumor
  • Cell Proliferation/drug effects
  • Cell Survival
  • Enzyme Activation
  • Gene Expression Profiling/methods
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma/enzymology
  • Humans
  • Naphthyridines/pharmacology
  • Tissue Array Analysis/methods
  • Tumor Microenvironment
  • Tumor Suppressor Protein p53/genetics


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