Targeting Protein Kinases in Blood Cancer: Focusing on CK1α and CK2.

Zaira Spinello, Anna Fregnani, Laura Quotti Tubi, Livio Trentin, Francesco Piazza, Sabrina Manni

International journal of molecular sciences 2021 Apr 02

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Disturbance of protein kinase activity may result in dramatic consequences that often lead to cancer development and progression. In tumors of blood origin, both tyrosine kinases and serine/threonine kinases are altered by different types of mutations, critically regulating cancer hallmarks. CK1α and CK2 are highly conserved, ubiquitously expressed and constitutively active pleiotropic kinases, which participate in multiple biological processes. The involvement of these kinases in solid and blood cancers is well documented. CK1α and CK2 are overactive in multiple myeloma, leukemias and lymphomas. Intriguingly, they are not required to the same degree for the viability of normal cells, corroborating the idea of "druggable" kinases. Different to other kinases, mutations on the gene encoding CK1α and CK2 are rare or not reported. Actually, these two kinases are outside the paradigm of oncogene addiction, since cancer cells' dependency on these proteins resembles the phenomenon of "non-oncogene" addiction. In this review, we will summarize the general features of CK1α and CK2 and the most relevant oncogenic and stress-related signaling nodes, regulated by kinase phosphorylation, that may lead to tumor progression. Finally, we will report the current data, which support the positioning of these two kinases in the therapeutic scene of hematological cancers.

Citation

Zaira Spinello, Anna Fregnani, Laura Quotti Tubi, Livio Trentin, Francesco Piazza, Sabrina Manni. Targeting Protein Kinases in Blood Cancer: Focusing on CK1α and CK2. International journal of molecular sciences. 2021 Apr 02;22(7)