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. 2022 Apr;126(7):994-1003.
doi: 10.1038/s41416-021-01616-2. Epub 2021 Nov 12.

CSNK2 in cancer: pathophysiology and translational applications

Scott W Strum  1 , Laszlo Gyenis  2 , David W Litchfield  3
Affiliations

CSNK2 in cancer: pathophysiology and translational applications

Scott W Strum et al. Br J Cancer. 2022 Apr.

Abstract

Protein kinase CSNK2 (CK2) is a pleiotropic serine/threonine kinase frequently dysregulated in solid and hematologic malignancies. To consolidate a wide range of biological and clinically oriented data from this unique kinase in cancer, this systematic review summarises existing knowledge from in vitro, in vivo and pre-clinical studies on CSNK2 across 24 different human cancer types. CSNK2 mRNA transcripts, protein levels and activity were found to be routinely upregulated in cancer, and commonly identified phosphotargets included AKT, STAT3, RELA, PTEN and TP53. Phenotypically, it frequently influenced evasion of apoptosis, enhancement of proliferation, cell invasion/metastasis and cell cycle control. Clinically, it held prognostic significance across 14 different cancers, and its inhibition in xenograft experiments resulted in a positive treatment response in 12. In conjunction with commentary on preliminary studies of CSNK2 inhibitors in humans, this review harmonises an extensive body of CSNK2 data in cancer and reinforces its emergence as an attractive target for cancer therapy. Continuing to investigate CSNK2 will be crucial to advancing our understanding of CSNK2 biology, and offers the promise of important new discoveries scientifically and clinically.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. CSNK2 phosphotargets, associated pathways, and CSNK2-regulated phenotypes identified in this review.
a Graphical summary of the pathways from which the five most commonly cited CSNK2 targets across all cancers were identified in this review: AKT, PTEN, RELA (NFkB), TP53 and STAT3. Red dotted arrows indicate negative regulation. Blue arrows indicate all other interactions. b The four most common biological phenotypes associated with CSNK2 in cancer, categorised by cancer hallmark [59] were: apoptosis (A), proliferation (P), cell cycle control (C) and invasion/metastasis (I). These four phenotypes were paired to the pathways from a if the pathway was an established regulator of this biological behaviour.
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