Liu Kai, Zheng Minying, Lu Rui, Du Jiaxing, Zhao Qi, Li Zugui, Li Yuwei, Zhang Shiwu
Department of Pathology, Tianjin Union Medical Center, Tianjin, 300121 People's Republic of China.
Department of Pathology, Tianjin Nankai Hospital, Tianjin, People's Republic of China.
Cancer Cell Int. 2020 Jun 3;20:213. doi: 10.1186/s12935-020-01304-w. eCollection 2020.
One of the most prominent features of tumor cells is uncontrolled cell proliferation caused by an abnormal cell cycle, and the abnormal expression of cell cycle-related proteins gives tumor cells their invasive, metastatic, drug-resistance, and anti-apoptotic abilities. Recently, an increasing number of cell cycle-associated proteins have become the candidate biomarkers for early diagnosis of malignant tumors and potential targets for cancer therapies. As an important cell cycle regulatory protein, Cell Division Cycle 25C (CDC25C) participates in regulating G2/M progression and in mediating DNA damage repair. CDC25C is a cyclin of the specific phosphatase family that activates the cyclin B1/CDK1 complex in cells for entering mitosis and regulates G2/M progression and plays an important role in checkpoint protein regulation in case of DNA damage, which can ensure accurate DNA information transmission to the daughter cells. The regulation of CDC25C in the cell cycle is affected by multiple signaling pathways, such as cyclin B1/CDK1, PLK1/Aurora A, ATR/CHK1, ATM/CHK2, CHK2/ERK, Wee1/Myt1, p53/Pin1, and ASK1/JNK-/38. Recently, it has evident that changes in the expression of CDC25C are closely related to tumorigenesis and tumor development and can be used as a potential target for cancer treatment. This review summarizes the role of CDC25C phosphatase in regulating cell cycle. Based on the role of CDC25 family proteins in the development of tumors, it will become a hot target for a new generation of cancer treatments.
肿瘤细胞最显著的特征之一是由异常细胞周期导致的不受控制的细胞增殖,细胞周期相关蛋白的异常表达赋予肿瘤细胞侵袭、转移、耐药和抗凋亡能力。最近,越来越多的细胞周期相关蛋白已成为恶性肿瘤早期诊断的候选生物标志物和癌症治疗的潜在靶点。作为一种重要的细胞周期调节蛋白,细胞分裂周期25C(CDC25C)参与调节G2/M期进程并介导DNA损伤修复。CDC25C是特定磷酸酶家族的一种细胞周期蛋白,可激活细胞中的细胞周期蛋白B1/周期蛋白依赖性激酶1(CDK1)复合物以进入有丝分裂,调节G2/M期进程,并在DNA损伤时的检查点蛋白调节中发挥重要作用,这可确保准确的DNA信息传递给子细胞。CDC25C在细胞周期中的调节受多种信号通路影响,如细胞周期蛋白B1/CDK1、Polo样激酶1(PLK1)/极光激酶A(Aurora A)、共济失调毛细血管扩张症突变基因(ATR)/细胞周期检查点激酶1(CHK1)、共济失调毛细血管扩张症突变(ATM)/CHK2、CHK2/细胞外信号调节激酶(ERK)、Wee1/髓鞘转录因子1(Myt1)、p53/肽基脯氨酰顺反异构酶NIMA相关激酶1(Pin1)和凋亡信号调节激酶1(ASK1)/应激活化蛋白激酶(JNK)/p38。最近,有证据表明CDC25C表达的变化与肿瘤发生和肿瘤发展密切相关,可作为癌症治疗的潜在靶点。本综述总结了CDC25C磷酸酶在调节细胞周期中的作用。基于CDC25家族蛋白在肿瘤发生中的作用,它将成为新一代癌症治疗的热门靶点。