Husain Kazim, Williamson Tanika T, Nelson Nadine, Ghansah Tomar
Department of Molecular Medicine, University of South Florida, Tampa, FL, USA.
Immunol Med. 2021 Sep;44(3):159-174. doi: 10.1080/25785826.2020.1843267. Epub 2020 Nov 9.
Protein kinase CK2, formally known as casein kinase II, is ubiquitously expressed and highly conserved serine/threonine or tyrosine kinase enzyme that regulates diverse signaling pathways responsible for cellular processes (i.e., cell proliferation and apoptosis) interactions with over 500 known substrates. The enzyme's physiological interactions and cellular functions have been widely studied, most notably in the blood and solid malignancies. CK2 has intrinsic role in carcinogenesis as overexpression of CK2 subunits (α, α`, and β) and deregulation of its activity have been linked to various forms of cancers. CK2 also has extrinsic role in cancer stroma or in the tumor microenvironment (TME) including the immune cells. However, very few research studies have focused on extrinsic role of CK2 in regulating immune responses as a therapeutic alternative for cancer. The following review discusses CK2's regulation of key signaling events [Nuclear factor kappa B (NF-κB), Janus kinase/signal transducer and activators of transcription (JAK/STAT), Hypoxia inducible factor-1alpha (HIF-1α), Cyclooygenase-2 (COX-2), Extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK), Notch, Protein kinase B/AKT, Ikaros and Wnt] that can influence the development and function of immune cells in cancer. Potential clinical trials using potent CK2 inhibitors will facilitate and improve the treatment of human malignancies.
蛋白激酶CK2，原称为酪蛋白激酶II，是一种广泛表达且高度保守的丝氨酸/苏氨酸或酪氨酸激酶，它调节负责细胞过程（如细胞增殖和凋亡）的多种信号通路，并与500多种已知底物相互作用。该酶的生理相互作用和细胞功能已得到广泛研究，尤其是在血液系统恶性肿瘤和实体瘤中。CK2在致癌过程中具有内在作用，因为CK2亚基（α、α`和β）的过表达及其活性失调与多种癌症有关。CK2在癌症基质或肿瘤微环境（TME）包括免疫细胞中也具有外在作用。然而，很少有研究关注CK2在调节免疫反应作为癌症治疗替代方案方面的外在作用。以下综述讨论了CK2对关键信号事件[核因子κB（NF-κB）、Janus激酶/信号转导和转录激活因子（JAK/STAT）、缺氧诱导因子-1α（HIF-1α）、环氧化酶-2（COX-2）、细胞外信号调节激酶/丝裂原活化蛋白激酶（ERK/MAPK）、Notch、蛋白激酶B/AKT、Ikaros和Wnt]的调节，这些事件可影响癌症中免疫细胞的发育和功能。使用强效CK2抑制剂的潜在临床试验将促进和改善人类恶性肿瘤的治疗。
