Department of Medicine, Western University, Schulich School of Medicine & Dentistry, London, ON, Canada.
Department of Biochemistry, Western University, Schulich School of Medicine & Dentistry, London, ON, Canada.
Br J Cancer. 2022 Apr;126(7):994-1003. doi: 10.1038/s41416-021-01616-2. Epub 2021 Nov 12.
Protein kinase CSNK2 (CK2) is a pleiotropic serine/threonine kinase frequently dysregulated in solid and hematologic malignancies. To consolidate a wide range of biological and clinically oriented data from this unique kinase in cancer, this systematic review summarises existing knowledge from in vitro, in vivo and pre-clinical studies on CSNK2 across 24 different human cancer types. CSNK2 mRNA transcripts, protein levels and activity were found to be routinely upregulated in cancer, and commonly identified phosphotargets included AKT, STAT3, RELA, PTEN and TP53. Phenotypically, it frequently influenced evasion of apoptosis, enhancement of proliferation, cell invasion/metastasis and cell cycle control. Clinically, it held prognostic significance across 14 different cancers, and its inhibition in xenograft experiments resulted in a positive treatment response in 12. In conjunction with commentary on preliminary studies of CSNK2 inhibitors in humans, this review harmonises an extensive body of CSNK2 data in cancer and reinforces its emergence as an attractive target for cancer therapy. Continuing to investigate CSNK2 will be crucial to advancing our understanding of CSNK2 biology, and offers the promise of important new discoveries scientifically and clinically.
蛋白激酶 CSNK2（CK2）是一种多功能丝氨酸/苏氨酸激酶，在实体瘤和血液恶性肿瘤中经常失调。为了整合来自这种独特激酶在癌症中的广泛的生物学和临床导向数据，本系统综述总结了来自 24 种不同人类癌症类型的体外、体内和临床前研究中关于 CSNK2 的现有知识。CSNK2 的 mRNA 转录本、蛋白水平和活性在癌症中经常上调，常见的磷酸化靶标包括 AKT、STAT3、RELA、PTEN 和 TP53。表型上，它经常影响细胞凋亡的逃逸、增殖的增强、细胞侵袭/转移和细胞周期的控制。临床上，它在 14 种不同的癌症中具有预后意义，在异种移植实验中抑制 CSNK2 导致 12 种癌症的治疗反应呈阳性。结合对 CSNK2 抑制剂在人类中的初步研究的评论，本综述协调了癌症中大量的 CSNK2 数据，并强化了其作为癌症治疗有吸引力的靶标的出现。继续研究 CSNK2 将对我们理解 CSNK2 生物学至关重要，并在科学和临床方面提供了重要的新发现的希望。
