[en] 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-kappaB hyperactivation in malignant gliomas is at best moderate, a delayed activation of NF-kappaB may associate with the therapeutic resistance of glioma cells to CK2 inhibition.
Disciplines :
Genetics & genetic processes
Author, co-author :
Dubois, Nadège ; Centre Hospitalier Universitaire de Liège - CHU > Département ULiège > Faculté de médecine
Willems, Marie
Nguyen-Khac, Minh-Tuan
Kroonen, Jerome
Goffart, Nicolas ; Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine
Deprez, Manuel
Bours, Vincent ; Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
Robe, Pierre ; Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Language :
English
Title :
Constitutive activation of casein kinase 2 in glioblastomas: Absence of class restriction and broad therapeutic potential.
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