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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Mini-Review Article

Current Progress and Perspectives of CDC20 in Female Reproductive Cancers

Author(s): Ke Ni* and Li Hong*

Volume 23, Issue 3, 2023

Published on: 26 April, 2022

Page: [193 - 199] Pages: 7

DOI: 10.2174/1573405618666220321130102

Price: $65

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Abstract

The cancers of the cervix, endometrium, ovary, and breast are great threats to women’s health. Cancer is characterized by the uncontrolled proliferation of cells and deregulated cell cycle progression is one of the main causes of malignancy. Agents targeting cell cycle regulators may have potential anti-tumor effects. CDC20 (cell division cycle 20 homologue) is a co-activator of the anaphase-promoting complex/cyclosome (APC/C) and thus acts as a mitotic regulator. In addition, CDC20 serves as a subunit of the mitotic checkpoint complex (MCC) whose function is to inhibit APC/C. Recently, higher expression of CDC20 has been reported in these cancers and was closely associated with their clinicopathological parameters, indicating CDC20 a potential target for cancer treatment that is worth further study. In the present review, we summarized current progress and put forward perspectives of CDC20 in female reproductive cancers.

Keywords: CDC20, cervical cancer, endometrial cancer, ovarian cancer, breast cancer, reproductive cancers.

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[1]
Eggersmann TK, Degenhardt T, Gluz O, Wuerstlein R, Harbeck N. CDK4/6 inhibitors expand the therapeutic options in breast cancer: Palbociclib, ribociclib and abemaciclib. BioDrugs 2019; 33(2): 125-35.
[http://dx.doi.org/10.1007/s40259-019-00337-6] [PMID: 30847853]
[2]
Hoppe T. Multiubiquitylation by E4 enzymes: ‘One size’ doesn’t fit all. Trends Biochem Sci 2005; 30(4): 183-7.
[http://dx.doi.org/10.1016/j.tibs.2005.02.004] [PMID: 15817394]
[3]
Hoeller D, Hecker CM, Dikic I. Ubiquitin and ubiquitin-like proteins in cancer pathogenesis. Nat Rev Cancer 2006; 6(10): 776-88.
[http://dx.doi.org/10.1038/nrc1994] [PMID: 16990855]
[4]
Nandi D, Tahiliani P, Kumar A, Chandu D. The ubiquitin-proteasome system. J Biosci 2006; 31(1): 137-55.
[http://dx.doi.org/10.1007/BF02705243] [PMID: 16595883]
[5]
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209-49.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[6]
Visintin R, Prinz S, Amon A. CDC20 and CDH1: A family of substrate-specific activators of APC-dependent proteolysis. Science 1997; 278(5337): 460-3.
[http://dx.doi.org/10.1126/science.278.5337.460] [PMID: 9334304]
[7]
Clute P, Pines J. Temporal and spatial control of cyclin B1 destruction in metaphase. Nat Cell Biol 1999; 1(2): 82-7.
[http://dx.doi.org/10.1038/10049] [PMID: 10559878]
[8]
Amador V, Ge S, Santamaría PG, Guardavaccaro D, Pagano M. APC/C(CDC20) controls the ubiquitin-mediated degradation of p21 in prometaphase. Mol Cell 2007; 27(3): 462-73.
[http://dx.doi.org/10.1016/j.molcel.2007.06.013] [PMID: 17679094]
[9]
Cui Y, Cheng X, Zhang C, et al. Degradation of the Human Mitotic Checkpoint Kinase Mps1 Is Cell Cycle-regulated by APC-C(CDC20) and APC-c(Cdh1). Ubiquitin Ligases J Biol Chem 2010; 285(43): 32988-98.
[http://dx.doi.org/10.1074/jbc.M110.140905] [PMID: 20729194]
[10]
Geley S, Kramer E, Gieffers C, Gannon J, Peters JM, Hunt T. Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint. J Cell Biol 2001; 153(1): 137-48.
[http://dx.doi.org/10.1083/jcb.153.1.137] [PMID: 11285280]
[11]
Gurden MDJ, Holland AJ, van Zon W, et al. CDC20 is required for the post-anaphase, KEN-dependent degradation of centromere protein F. J Cell Sci 2010; 123(Pt 3): 321-30.
[http://dx.doi.org/10.1242/jcs.062075] [PMID: 20053638]
[12]
Hayes MJ, Kimata Y, Wattam SL, et al. Early mitotic degradation of Nek2A depends on CDC20-independent interaction with the APC/C. Nat Cell Biol 2006; 8(6): 607-14.
[http://dx.doi.org/10.1038/ncb1410] [PMID: 16648845]
[13]
Sudakin V, Chan GKT, Yen TJ. Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. J Cell Biol 2001; 154(5): 925-36.
[http://dx.doi.org/10.1083/jcb.200102093] [PMID: 11535616]
[14]
Lara-Gonzalez P, Westhorpe FG, Taylor SS. The spindle assembly checkpoint. Curr Biol 2012; 22(22): R966-80.
[http://dx.doi.org/10.1016/j.cub.2012.10.006] [PMID: 23174302]
[15]
Cory S, Adams JM. The Bcl2 family: Regulators of the cellular life-or-death switch. Nat Rev Cancer 2002; 2(9): 647-56.
[http://dx.doi.org/10.1038/nrc883] [PMID: 12209154]
[16]
Wan L, Tan M, Yang J, et al. APC(CDC20) suppresses apoptosis through targeting Bim for ubiquitination and destruction. Dev Cell 2014; 29(4): 377-91.
[http://dx.doi.org/10.1016/j.devcel.2014.04.022] [PMID: 24871945]
[17]
Harley ME, Allan LA, Sanderson HS, Clarke PR. Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its CDC20-dependent destruction during mitotic arrest. EMBO J 2010; 29(14): 2407-20.
[http://dx.doi.org/10.1038/emboj.2010.112] [PMID: 20526282]
[18]
Wang R, Li KM, Zhou CH, Xue JL, Ji CN, Chen JZ. CDC20 mediates D-box-dependent degradation of Sp100. Biochem Biophys Res Commun 2011; 415(4): 702-6.
[http://dx.doi.org/10.1016/j.bbrc.2011.10.146] [PMID: 22086178]
[19]
Yang Y, Kim AH, Yamada T, et al. A CDC20-APC ubiquitin signaling pathway regulates presynaptic differentiation. Science 2009; 326(5952): 575-8.
[http://dx.doi.org/10.1126/science.1177087] [PMID: 19900895]
[20]
Kim AH, Puram SV, Bilimoria PM, et al. A centrosomal CDC20-APC pathway controls dendrite morphogenesis in postmitotic neurons. Cell 2009; 136(2): 322-36.
[http://dx.doi.org/10.1016/j.cell.2008.11.050] [PMID: 19167333]
[21]
Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. Lancet 2013; 382(9895): 889-99.
[http://dx.doi.org/10.1016/S0140-6736(13)60022-7] [PMID: 23618600]
[22]
Rajkumar T, Sabitha K, Vijayalakshmi N, et al. Identification and validation of genes involved in cervical tumourigenesis. BMC Cancer 2011; 11(1): 80.
[http://dx.doi.org/10.1186/1471-2407-11-80] [PMID: 21338529]
[23]
Kim Y, Choi JW, Lee JH, Kim YS. MAD2 and CDC20 are upregulated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix. Int J Gynecol Pathol 2014; 33(5): 517-23.
[http://dx.doi.org/10.1097/PGP.0000000000000082] [PMID: 25083970]
[24]
Gayyed MF, El-Maqsoud NM, Tawfiek ER, El Gelany SA, Rahman MF. A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: Its correlation with tumor grade and stage. Tumour Biol 2016; 37(1): 749-62.
[http://dx.doi.org/10.1007/s13277-015-3808-1] [PMID: 26245990]
[25]
Espinosa AM, Alfaro A, Roman-Basaure E, et al. Mitosis is a source of potential markers for screening and survival and therapeutic targets in cervical cancer. PLoS One 2013; 8(2): e55975.
[http://dx.doi.org/10.1371/journal.pone.0055975] [PMID: 23405241]
[26]
Patel D, McCance DJ. Compromised spindle assembly checkpoint due to altered expression of Ubch10 and CDC20 in human papillomavirus type 16 E6- and E7-expressing keratinocytes. J Virol 2010; 84(21): 10956-64.
[http://dx.doi.org/10.1128/JVI.00259-10] [PMID: 20739533]
[27]
Bellanger S, Blachon S, Mechali F, Bonne-Andrea C, Thierry F. High-risk but not low-risk HPV E2 proteins bind to the APC activators Cdh1 and CDC20 and cause genomic instability. Cell Cycle 2005; 4(11): 1608-15.
[http://dx.doi.org/10.4161/cc.4.11.2123] [PMID: 16222116]
[28]
Tan CL, Teissier S, Gunaratne J, Quek LS, Bellanger S. Stranglehold on the spindle assembly checkpoint: The human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy. Cell Cycle 2015; 14(9): 1459-70.
[http://dx.doi.org/10.1080/15384101.2015.1021519] [PMID: 25789401]
[29]
Vadlamudi Y, Dey DK, Kang SC. Emerging multi-cancer regulatory role of ESRP1: Orchestration of alternative splicing to control EMT. Curr Cancer Drug Targets 2020; 20(9): 654-65.
[http://dx.doi.org/10.2174/1568009620666200621153831] [PMID: 32564755]
[30]
Chen ZH, Jing YJ, Yu JB, et al. ESRP1 induces cervical cancer cell g1-phase arrest via regulating cyclin A2 mRNA stability. Int J Mol Sci 2019; 20(15): E3705.
[http://dx.doi.org/10.3390/ijms20153705] [PMID: 31362365]
[31]
McAlpine JN, Temkin SM, Mackay HJ. Endometrial cancer: Not your grandmother’s cancer. Cancer 2016; 122(18): 2787-98.
[http://dx.doi.org/10.1002/cncr.30094] [PMID: 27308732]
[32]
Huo X, Sun H, Cao D, et al. Identification of prognosis markers for endometrial cancer by integrated analysis of DNA methylation and RNA-Seq data. Sci Rep 2019; 9(1): 9924.
[http://dx.doi.org/10.1038/s41598-019-46195-8] [PMID: 31289358]
[33]
Ledermann JA, Embleton AC, Raja F, et al. Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2016; 387(10023): 1066-74.
[http://dx.doi.org/10.1016/S0140-6736(15)01167-8] [PMID: 27025186]
[34]
Ouellet V, Guyot MC, Le Page C, et al. Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer. Int J Cancer 2006; 119(3): 599-607.
[http://dx.doi.org/10.1002/ijc.21902] [PMID: 16572426]
[35]
Sun Q, Zhao H, Zhang C, et al. Gene co-expression network reveals shared modules predictive of stage and grade in serous ovarian cancers. Oncotarget 2017; 8(26): 42983-96.
[http://dx.doi.org/10.18632/oncotarget.17785] [PMID: 28562334]
[36]
Sun X, Liu Q, Huang J, Diao G, Liang Z. Transcriptome-based stemness indices analysis reveals platinum-based chemo-theraputic response indicators in advanced-stage serous ovarian cancer. Bioengineered 2021; 12(1): 3753-71.
[http://dx.doi.org/10.1080/21655979.2021.1939514] [PMID: 34266348]
[37]
Yang D, He Y, Wu B, et al. Integrated bioinformatics analysis for the screening of hub genes and therapeutic drugs in ovarian cancer. J Ovarian Res 2020; 13(1): 10.
[http://dx.doi.org/10.1186/s13048-020-0613-2] [PMID: 31987036]
[38]
Fei H, Chen S, Xu C. Bioinformatics analysis of gene expression profile of serous ovarian carcinomas to screen key genes and pathways. J Ovarian Res 2020; 13(1): 82.
[http://dx.doi.org/10.1186/s13048-020-00680-1] [PMID: 32693821]
[39]
Dong C, Tian X, He F, et al. Integrative analysis of key candidate genes and signaling pathways in ovarian cancer by bioinformatics. J Ovarian Res 2021; 14(1): 92.
[http://dx.doi.org/10.1186/s13048-021-00837-6] [PMID: 34253236]
[40]
Li DF, Tulahong A, Uddin MN, Zhao H, Zhang H. Meta-analysis identifying epithelial-derived transcriptomes predicts poor clinical outcome and immune infiltrations in ovarian cancer. Math Biosci Eng 2021; 18(5): 6527-51.
[PMID: 34517544]
[41]
Kang YM, Lan A, Huang YH, Hsu KM, Chao Y, Lan KL. Identification of key genes and pathways associated with topotecan treatment using multiple bioinformatics tools. J Chin Med Assoc 2020; 83(5): 446-53.
[http://dx.doi.org/10.1097/JCMA.0000000000000313] [PMID: 32243271]
[42]
Song C, Lowe VJ, Lee S. Inhibition of CDC20 suppresses the metastasis in triple negative breast cancer (TNBC). Breast Cancer 2021; 28(5): 1073-86.
[http://dx.doi.org/10.1007/s12282-021-01242-z] [PMID: 33813687]
[43]
Yuan B, Xu Y, Woo JH, et al. Increased expression of mitotic checkpoint genes in breast cancer cells with chromosomal instability. Clin Cancer Res 2006; 12(2): 405-10.
[http://dx.doi.org/10.1158/1078-0432.CCR-05-0903] [PMID: 16428479]
[44]
Alfarsi LH, Ansari RE, Craze ML, et al. CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy. Breast Cancer Res Treat 2019; 178(3): 535-44.
[http://dx.doi.org/10.1007/s10549-019-05420-8] [PMID: 31471836]
[45]
Cheng L, Huang YZ, Chen WX, et al. Cell division cycle proteinising prognostic biomarker of breast cancer. Biosci Rep 2020; 40(5): BSR20191227.
[http://dx.doi.org/10.1042/BSR20191227] [PMID: 32285914]
[46]
Hong Z, Wang Q, Hong C, et al. Identification of seven cell cycle-related genes with unfavorable prognosis and construction of their TF-miRNA-mRNA regulatory network in Breast Cancer. J Cancer 2021; 12(3): 740-53.
[http://dx.doi.org/10.7150/jca.48245] [PMID: 33403032]
[47]
Wu J, Lv Q, Huang H, Zhu M, Meng D. Screening and identification of key biomarkers in inflammatory breast cancer through integrated bioinformatic analyses. Genet Test Mol Biomarkers 2020; 24(8): 484-91.
[http://dx.doi.org/10.1089/gtmb.2020.0047] [PMID: 32598242]
[48]
Wang N, Zhang H, Li D, Jiang C, Zhao H, Teng Y. Identification of novel biomarkers in breast cancer via integrated bioinformatics analysis and experimental validation. Bioengineered 2021; 12(2): 12431-46.
[http://dx.doi.org/10.1080/21655979.2021.2005747] [PMID: 34895070]
[49]
Cheng S, Castillo V, Sliva D. CDC20 associated with cancer metastasis and novel mushroom-derived CDC20 inhibitors with antimetastatic activity. Int J Oncol 2019; 54(6): 2250-6.
[http://dx.doi.org/10.3892/ijo.2019.4791] [PMID: 31081056]
[50]
Parmar MB, Aliabadi HM, Mahdipoor P, et al. Targeting cell cycle proteins in breast cancer cells with sirna by using lipid-substituted polyethylenimines. Front Bioeng Biotechnol 2015; 3: 14.
[http://dx.doi.org/10.3389/fbioe.2015.00014] [PMID: 25763370]
[51]
Zhang X. Identification of potential prognostic markers associated with lung metastasis in breast cancer by coexpression network analysis. Cancer Biomark 2021; 1-12.
[http://dx.doi.org/10.3233/CBM-210199] [PMID: 34459389]
[52]
Karra H, Repo H, Ahonen I, et al. CDC20 and securin overexpression predict short-term breast cancer survival. Br J Cancer 2014; 110(12): 2905-13.
[http://dx.doi.org/10.1038/bjc.2014.252] [PMID: 24853182]
[53]
Paul D, Ghorai S, Dinesh US, Shetty P, Chattopadhyay S, Santra MK. CDC20 directs proteasome-mediated degradation of the tumor suppressor SMAR1 in higher grades of cancer through the anaphase promoting complex. Cell Death Dis 2017; 8(6): e2882.
[http://dx.doi.org/10.1038/cddis.2017.270] [PMID: 28617439]
[54]
Bellati F, Napoletano C, Ruscito I, et al. Past, present and future strategies of immunotherapy in gynecological malignancies. Curr Mol Med 2013; 13(4): 648-69.
[http://dx.doi.org/10.2174/1566524011313040014] [PMID: 22934850]
[55]
Wang L, Zhang J, Wan L, Zhou X, Wang Z, Wei W. Targeting CDC20 as a novel cancer therapeutic strategy. Pharmacol Ther 2015; 151: 141-51.
[http://dx.doi.org/10.1016/j.pharmthera.2015.04.002] [PMID: 25850036]
[56]
Zhang L, Yang B, Zhou K, et al. Potential therapeutic mechanism of genistein in breast cancer involves inhibition of cell cycle regulation. Mol Med Rep 2015; 11(3): 1820-6.
[http://dx.doi.org/10.3892/mmr.2014.2907] [PMID: 25385471]
[57]
Nagalingam A, Kuppusamy P, Singh SV, Sharma D, Saxena NK. Mechanistic elucidation of the antitumor properties of withaferin a in breast cancer. Cancer Res 2014; 74(9): 2617-29.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-2081] [PMID: 24732433]
[58]
Jiang J, Jedinak A, Sliva D. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA. Biochem Biophys Res Commun 2011; 415(2): 325-9.
[http://dx.doi.org/10.1016/j.bbrc.2011.10.055] [PMID: 22033405]
[59]
Jiang J, Thyagarajan-Sahu A, Krchňák V, Jedinak A, Sandusky GE, Sliva D. NAHA, a novel hydroxamic acid-derivative, inhibits growth and angiogenesis of breast cancer in vitro and in vivo. PLoS One 2012; 7(3): e34283.
[http://dx.doi.org/10.1371/journal.pone.0034283] [PMID: 22479587]
[60]
Yamashita N, Yoshizuka A, Kase A, et al. Activation of the aryl hydrocarbon receptor by 3-methylcholanthrene, but not by indirubin, suppresses mammosphere formation via downregulation of CDC20 expression in breast cancer cells. Biochem Biophys Res Commun 2021; 570: 131-6.
[http://dx.doi.org/10.1016/j.bbrc.2021.07.047] [PMID: 34280616]
[61]
Egorova A, Pyankov I, Maretina M, Baranov V, Kiselev A. Peptide nanoparticle-mediated combinatorial delivery of cancer-related sirnas for synergistic anti-proliferative activity in triple negative breast cancer cells. Pharmaceuticals (Basel) 2021; 14(10): 957.
[http://dx.doi.org/10.3390/ph14100957] [PMID: 34681181]
[62]
Liu N, Wang X, Zhu Z, et al. Selected ideal natural ligand against TNBC by inhibiting CDC20, using bioinformatics and molecular biology. Aging (Albany NY) 2021; 13(20): 23702-25.
[http://dx.doi.org/10.18632/aging.203642] [PMID: 34686627]
[63]
Li M, Li A, Zhou S, Lv H, Yang W. SPAG5 upregulation contributes to enhanced c-MYC transcriptional activity via interaction with c-MYC binding protein in triple-negative breast cancer. J Hematol Oncol 2019; 12(1): 14.
[http://dx.doi.org/10.1186/s13045-019-0700-2] [PMID: 30736840]
[64]
Kim HS, Vassilopoulos A, Wang RH, et al. SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell 2011; 20(4): 487-99.
[http://dx.doi.org/10.1016/j.ccr.2011.09.004] [PMID: 22014574]
[65]
Kidokoro T, Tanikawa C, Furukawa Y, Katagiri T, Nakamura Y, Matsuda K. CDC20, a potential cancer therapeutic target, is negatively regulated by p53. Oncogene 2008; 27(11): 1562-71.
[http://dx.doi.org/10.1038/sj.onc.1210799] [PMID: 17873905]
[66]
Zeng X, Sigoillot F, Gaur S, et al. Pharmacologic inhibition of the anaphase-promoting complex induces a spindle checkpoint-dependent mitotic arrest in the absence of spindle damage. Cancer Cell 2010; 18(4): 382-95.
[http://dx.doi.org/10.1016/j.ccr.2010.08.010] [PMID: 20951947]
[67]
Wang Z, Wan L, Zhong J, et al. CDC20: A potential novel therapeutic target for cancer treatment. Curr Pharm Des 2013; 19(18): 3210-4.
[http://dx.doi.org/10.2174/1381612811319180005] [PMID: 23151139]
[68]
Penas C, Ramachandran V, Ayad NG. The APC/C Ubiquitin Ligase: From Cell Biology to Tumorigenesis. Front Oncol 2012; 1: 60.
[http://dx.doi.org/10.3389/fonc.2011.00060] [PMID: 22655255]

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