title: Targeting Cdc20 as a novel cancer therapeutic strategy.
abstract: 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, APC(Cdc20) and APC(Cdh1), 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.
authors: The Cyrus Tang Hematology Center Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou 215123, China; Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou 215123, China.
authors: Lixia
authors: L
authors: Wang
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, MA 02215, USA.
authors: Jinfang
authors: J
authors: Zhang
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, MA 02215, USA.
authors: Lixin
authors: L
authors: Wan
authors: The Cyrus Tang Hematology Center Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou 215123, China; Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou 215123, China.
authors: Xiuxia
authors: X
authors: Zhou
authors: The Cyrus Tang Hematology Center Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou 215123, China; Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou 215123, China. Electronic address: zhiweichina@126.com.
authors: Zhiwei
authors: Z
authors: Wang
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, MA 02215, USA. Electronic address: wwei2@bidmc.harvard.edu.
authors: Wenyi
authors: W
authors: Wei
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D001921:Brain / Q000166:cytology / Q000502:physiology; D064199:Cdc20 Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002453:Cell Cycle; D002454:Cell Differentiation; D002923:Cilia / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000502:physiology; D054875:Ubiquitination
chemical_list: D000970:Antineoplastic Agents; D064199:Cdc20 Proteins; C577488:CDC20 protein, human
keywords: Cancer; Cdc20; Drug; E3 ligase; SCF; Target