Targeting Cdc20 as a novel cancer therapeutic strategy.
Targeting Cdc20 as a novel cancer therapeutic strategy.
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DOI：
10.1016/j.pharmthera.2015.04.002
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发表时间：
2015-07
影响因子：
13.5
通讯作者：
Wei, Wenyi
中科院分区：
文献类型：
--
作者：
Wang, Lixia;Zhang, Jinfang;Wan, Lixin;Zhou, Xiuxia;Wang, Zhiwei;Wei, Wenyi
后期促进复合体（APC，也称为APC/C）通过形成两个密切相关但功能不同的E3泛素连接酶亚复合体APCCdc20和APCCdh1来调节细胞周期进程。新的证据已经开始揭示Cdc20和Cdh1在肿瘤发生中具有相反的功能。具体来说，Cdh1的功能主要是作为肿瘤抑制因子，而Cdc20表现出致癌功能，这表明Cdc20可能是对抗人类癌症的一个有希望的治疗靶点。然而，它们在肿瘤发生方面的差异的确切的潜在分子机制在很大程度上仍然未知。因此，本文就Cdc20的下游底物及Cdc20在细胞周期进程、细胞凋亡、纤毛脱落和脑发育中的关键功能进行综述。此外，我们简要描述了Cdc20的上游调控因子和Cdc20在多种人类恶性肿瘤中的致癌作用。此外，我们总结了多种药物Cdc20抑制剂，包括TAME和Apcin，及其潜在的临床益处。综上所述，开发特异性Cdc20抑制剂可能是治疗Cdc20表达升高的人类癌症的新策略。
The Anaphase Promoting Complex (APC, also called APC/C) regulates cell cycle progression by forming two closely related, but functionally distinct E3 ubiquitin ligase sub-complexes, APCCdc20 and APCCdh1, respectively. Emerging evidence has begun to reveal that Cdc20 and Cdh1 have opposing functions in tumorigenesis. Specifically, Cdh1 functions largely as a tumor suppressor, whereas Cdc20 exhibits an oncogenic function, suggesting that Cdc20 could be a promising therapeutic target for combating human cancer. However, the exact underlying molecular mechanisms accounting for their differences in tumorigenesis remain largely unknown. Therefore, in this review, we summarize the downstream substrates of Cdc20 and the critical functions of Cdc20 in cell cycle progression, apoptosis, ciliary disassembly and brain development. Moreover, we briefly describe the upstream regulators of Cdc20 and the oncogenic role of Cdc20 in a variety of human malignancies. Furthermore, we summarize multiple pharmacological Cdc20 inhibitors including TAME and Apcin, and their potential clinical benefits. Taken together, development of specific Cdc20 inhibitors could be a novel strategy for the treatment of human cancers with elevated Cdc20 expression.
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DOI：
10.1083/jcb.201211019
发表时间：
2013-06-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Clijsters L;Ogink J;Wolthuis R
通讯作者：
Wolthuis R
DOI：
10.1016/j.bbamcr.2013.02.028
发表时间：
2014-01
影响因子：
5.1
作者：
Bassermann, Florian;Eichner, Ruth;Pagano, Michele
通讯作者：
Pagano, Michele
影响因子：
11.4
作者：
Akiyama, T;Bouillet, P;Tanaka, S
通讯作者：
Tanaka, S
影响因子：
5.3
作者：
Castro, A;Vigneron, S;Lorca, T
通讯作者：
Lorca, T
影响因子：
64.8
作者：
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通讯作者：
Pagano, M