Protein Kinase CK2 in Cancer Biology

Protein kinase CK2 is a constitutively active serine/threonine kinase present in all eukaryotic cells, composed of two catalytic (α and αʹ) and two regulatory (β) subunits. It phosphorylates hundreds of substrates, integrating signals that govern cell proliferation, survival, DNA repair, apoptosis resistance and angiogenesis. In many tumours CK2 activity and expression are elevated, contributing to oncogenic signalling through pathways such as PI3K/Akt/mTOR, NF-κB, Wnt/β-catenin and JAK/STAT. CK2 also modulates the stability and function of tumour suppressors, including p53 and SALL2, as well as the biogenesis of oncogenic microRNAs. Its broad substrate specificity and subcellular localisation allow CK2 to orchestrate networks of post-translational modifications that sustain malignant hallmarks. The availability of selective ATP-competitive inhibitors has enabled preclinical demonstration of impaired growth, induced apoptosis and sensitisation to chemotherapy in diverse cancer models. Clinical evaluation of CK2 inhibitors is underway, highlighting both the promise and challenges of targeting a pleiotropic kinase in precision oncology.

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Protein Kinase CK2 in Cancer Biology publication trend

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Technical terms

Serine/threonine kinase: Enzyme that adds a phosphate group to serine or threonine residues on proteins, modulating their activity.

Phosphorylation: Covalent attachment of a phosphate group to a protein, often altering its function, localisation or stability.

Proteasome: Multi-subunit complex responsible for degrading ubiquitinated proteins, regulating protein turnover.

MicroRNA: Short non-coding RNA molecule that binds target messenger RNAs to suppress translation or promote degradation.

Oncomir: A microRNA with oncogenic function that promotes tumour growth and survival.

Orthotopic xenograft model: Animal model in which human cancer cells are implanted into the corresponding organ site to mimic tumour behaviour in vivo.

References

1. Casein kinase 2 phosphorylates and induces the SALL2 tumor suppressor degradation in colon cancer cells. Cell Death & Disease (2024).
2. Impact of protein kinase CK2 downregulation and inhibition on oncomir clusters 17 ~ 92 and 106b ~ 25 in prostate, breast, and head and neck cancers. Molecular Medicine (2024).
3. CK2 in Cancer: Cellular and Biochemical Mechanisms and Potential Therapeutic Target. Pharmaceuticals (2017).