CSNK2 in cancer: pathophysiology and translational applications.

CSNK2 in cancer: pathophysiology and translational applications.
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DOI:
10.1038/s41416-021-01616-2
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发表时间:
2022-04
影响因子:
8.8
通讯作者:
Litchfield DW
Litchfield DW
中科院分区:
医学1区
文献类型:
--
作者:
Strum SW;Gyenis L;Litchfield DW

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蛋白激酶 CSNK2 (CK2) 是一种多效性丝氨酸/苏氨酸激酶,在实体瘤和血液恶性肿瘤中经常失调。为了整合这种独特的癌症激酶的广泛生物学和临床导向数据,本系统综述总结了 24 种不同人类癌症类型的 CSNK2 体外、体内和临床前研究的现有知识。研究发现,CSNK2 mRNA 转录本、蛋白质水平和活性在癌症中通常上调,常见的磷酸靶标包括 AKT、STAT3、RELA、PTEN 和 TP53。在表型上,它经常影响细胞凋亡的逃避、增殖的增强、细胞侵袭/转移和细胞周期控制。在临床上,它对 14 种不同的癌症具有预后意义,并且它在异种移植实验中的抑制导致了 12 种癌症的积极治疗反应。结合对人类 CSNK2 抑制剂的初步研究的评论,这篇综述协调了癌症中广泛的 CSNK2 数据,并强化了它作为癌症治疗的一个有吸引力的靶点的出现。继续研究 CSNK2 对于增进我们对 CSNK2 生物学的理解至关重要,并有望在科学和临床上取得重要的新发现。
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.
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