Ghafouri-Fard Soudeh, Khoshbakht Tayyebeh, Hussen Bashdar Mahmud, Dong Peixin, Gassler Nikolaus, Taheri Mohammad, Baniahmad Aria, Dilmaghani Nader Akbari
Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cancer Cell Int. 2022 Oct 20;22(1):325. doi: 10.1186/s12935-022-02747-z.
The Cyclin-dependent kinase (CDK) class of serine/threonine kinases has crucial roles in the regulation of cell cycle transition and is mainly involved in the pathogenesis of cancers. The expression of CDKs is controlled by a complex regulatory network comprised of genetic and epigenetic mechanisms, which are dysregulated during the progression of cancer. The abnormal activation of CDKs results in uncontrolled cancer cell proliferation and the induction of cancer stem cell characteristics. The levels of CDKs can be utilized to predict the prognosis and treatment response of cancer patients, and further understanding of the function and underlying mechanisms of CDKs in human tumors would pave the way for future cancer therapies that effectively target CDKs. Defects in the regulation of cell cycle and mutations in the genes coding cell-cycle regulatory proteins lead to unrestrained proliferation of cells leading to formation of tumors. A number of treatment modalities have been designed to combat dysregulation of cell cycle through affecting expression or activity of CDKs. However, effective application of these methods in the clinical settings requires recognition of the role of CDKs in the progression of each type of cancer, their partners, their interactions with signaling pathways and the effects of suppression of these kinases on malignant features. Thus, we designed this literature search to summarize these findings at cellular level, as well as in vivo and clinical levels.
细胞周期蛋白依赖性激酶(CDK)类丝氨酸/苏氨酸激酶在细胞周期转换的调控中起关键作用,且主要参与癌症的发病机制。CDK的表达受一个由遗传和表观遗传机制组成的复杂调控网络控制,该网络在癌症进展过程中失调。CDK的异常激活导致癌细胞不受控制地增殖,并诱导癌症干细胞特征。CDK的水平可用于预测癌症患者的预后和治疗反应,进一步了解CDK在人类肿瘤中的功能和潜在机制将为未来有效靶向CDK的癌症治疗铺平道路。细胞周期调控缺陷和编码细胞周期调节蛋白的基因突变会导致细胞不受控制地增殖,从而形成肿瘤。已经设计了多种治疗方式,通过影响CDK的表达或活性来对抗细胞周期失调。然而,要在临床环境中有效应用这些方法,需要认识到CDK在每种癌症进展中的作用、其伙伴、它们与信号通路的相互作用以及抑制这些激酶对恶性特征的影响。因此,我们设计了这次文献检索,以在细胞水平以及体内和临床水平上总结这些发现。