Department of Medicine, Hematology Section, University of Padova, Via N. Giustiniani 2, 35128 Padova, Italy.
Veneto Institute of Molecular Medicine, Via G. Orus 2, 35129 Padova, Italy.
Int J Mol Sci. 2021 Apr 2;22(7):3716. doi: 10.3390/ijms22073716.
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.
蛋白激酶活性的紊乱可能导致严重的后果，常常导致癌症的发生和发展。在血液来源的肿瘤中，酪氨酸激酶和丝氨酸/苏氨酸激酶都被不同类型的突变所改变，这些突变对癌症的标志性特征起着关键性的调节作用。CK1α 和 CK2 是高度保守、广泛表达和组成性激活的多功能激酶，参与多种生物学过程。这些激酶在实体瘤和血液癌中的参与已得到充分证实。CK1α 和 CK2 在多发性骨髓瘤、白血病和淋巴瘤中过度活跃。有趣的是，它们对于正常细胞的存活并非必需到相同程度，这证实了“可成药”激酶的观点。与其他激酶不同，编码 CK1α 和 CK2 的基因突变很少或没有报道。实际上，这两种激酶不在癌基因成瘾的范例之外，因为癌细胞对这些蛋白质的依赖性类似于“非癌基因”成瘾的现象。在这篇综述中，我们将总结 CK1α 和 CK2 的一般特征，以及最相关的致癌和应激相关信号节点，这些节点受激酶磷酸化的调节，可能导致肿瘤的进展。最后，我们将报告支持将这两种激酶定位在血液恶性肿瘤治疗领域的现有数据。
