Zonta Francesca, Borgo Christian, Quezada Meza Camila Paz, Masgras Ionica, Rasola Andrea, Salvi Mauro, Pinna Lorenzo A, Ruzzene Maria
Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy.
CNR Neuroscience Institute, 35131 Padova, Italy.
Cells. 2021 Jan 18;10(1):181. doi: 10.3390/cells10010181.
CK2 is a Ser/Thr protein kinase overexpressed in many cancers. It is usually present in cells as a tetrameric enzyme, composed of two catalytic (α or α') and two regulatory (β) subunits, but it is active also in its monomeric form, and the specific role of the different isoforms is largely unknown. CK2 phosphorylates several substrates related to the uncontrolled proliferation, motility, and survival of cancer cells. As a consequence, tumor cells are addicted to CK2, relying on its activity more than healthy cells for their life, and exploiting it for developing multiple oncological hallmarks. However, little is known about CK2 contribution to the metabolic rewiring of cancer cells. With this study we aimed at shedding some light on it, especially focusing on the CK2 role in the glycolytic onco-phenotype. By analyzing neuroblastoma and osteosarcoma cell lines depleted of either one (α) or the other (α') CK2 catalytic subunit, we also aimed at disclosing possible pro-tumor functions which are specific of a CK2 isoform. Our results suggest that both CK2 α and α' contribute to cell proliferation, survival and tumorigenicity. The analyzed metabolic features disclosed a role of CK2 in tumor metabolism, and suggest prominent functions for CK2 α isoform. Results were also confirmed by CK2 pharmacological inhibition. Overall, our study provides new information on the mechanism of cancer cells addiction to CK2 and on its isoform-specific functions, with fundamental implications for improving future therapeutic strategies based on CK2 targeting.
CK2是一种在多种癌症中过表达的丝氨酸/苏氨酸蛋白激酶。它通常以四聚体酶的形式存在于细胞中，由两个催化亚基（α或α'）和两个调节亚基（β）组成，但它的单体形式也具有活性，不同异构体的具体作用在很大程度上尚不清楚。CK2可磷酸化多种与癌细胞不受控制的增殖、运动和存活相关的底物。因此，肿瘤细胞对CK2成瘾，其生存比健康细胞更依赖CK2的活性，并利用它来形成多种肿瘤学特征。然而，关于CK2对癌细胞代谢重编程的贡献知之甚少。通过这项研究，我们旨在对此进行一些阐释，尤其关注CK2在糖酵解肿瘤表型中的作用。通过分析缺失CK2催化亚基之一（α）或另一个（α'）的神经母细胞瘤和骨肉瘤细胞系，我们还旨在揭示特定CK2异构体特有的可能的促肿瘤功能。我们的结果表明，CK2α和α'都对细胞增殖、存活和致瘤性有贡献。所分析的代谢特征揭示了CK2在肿瘤代谢中的作用，并表明CK2α异构体具有突出功能。CK2的药理学抑制也证实了这些结果。总体而言，我们的研究提供了关于癌细胞对CK2成瘾机制及其异构体特异性功能的新信息，对改进基于靶向CK2的未来治疗策略具有重要意义。
