Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

USP48 Sustains Chemoresistance and Metastasis in Ovarian Cancer

Author(s): Xuemeng Lei, Xukun Li, Hongyan Chen and Zhihua Liu*

Volume 20, Issue 9, 2020

Page: [689 - 699] Pages: 11

DOI: 10.2174/1568009620666200503045400

Price: $65

Abstract

Background: Ubiquitin specific protease 48 (USP48) is a member of the deubiquitinating enzymes (DUBs) family. However, the function of USP48 in ovarian cancer remains unclear.

Objective: The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation.

Methods: After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells. The subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly increases responsiveness to CBP, and alleviates the metastasis in vivo. Meanwhile, USP48 deficiency results in the improved survival of mice.

Results: Finally, the analysis of clinical samples and the TCGA and Kaplan-Meier Plot database revealed that the high expression of USP48 in ovarian cancer patients is associated with poor survival and resistance to CBP therapy.

Conclusion: In summary, USP48 may be a potential therapeutic target for ovarian cancer patients.

Keywords: Apoptosis, chemoresistance, DUBs, metastasis, ovarian cancer, USP48.

« Previous Next »
Graphical Abstract

[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin., 2018, 68(1), 7-30.
[http://dx.doi.org/10.3322/caac.21442] [PMID: 29313949]
[2]
Leong, H.S.; Galletta, L.; Etemadmoghadam, D.; George, J.; Köbel, M.; Ramus, S.J.; Bowtell, D. Australian ovarian cancer study. Efficient molecular subtype classification of high-grade serous ovarian cancer. J. Pathol., 2015, 236(3), 272-277.
[http://dx.doi.org/10.1002/path.4536] [PMID: 25810134]
[3]
Zhang, A.W.; McPherson, A.; Milne, K.; Kroeger, D.R.; Hamilton, P.T.; Miranda, A.; Funnell, T.; Little, N.; de Souza, C.P.E.; Laan, S.; LeDoux, S.; Cochrane, D.R.; Lim, J.L.P.; Yang, W.; Roth, A.; Smith, M.A.; Ho, J.; Tse, K.; Zeng, T.; Shlafman, I.; Mayo, M.R.; Moore, R.; Failmezger, H.; Heindl, A.; Wang, Y.K.; Bashashati, A.; Grewal, D.S.; Brown, S.D.; Lai, D.; Wan, A.N.C.; Nielsen, C.B.; Huebner, C.; Tessier-Cloutier, B.; Anglesio, M.S.; Bouchard-Cote, A.; Yuan, Y.; Wasserman, W.W.; Gilks, C.B.; Karnezis, A.N.; Aparicio, S.; McAlpine, J.N.; Huntsman, D.G.; Holt, R.A.; Nelson, B.H.; Shah, S.P. interfaces of malignant and immunologic clonal dynamics in ovarian cancer. Cell, 2018, 173(7), 1755-1769.
[http://dx.doi.org/10.1016/j.cell.2018.03.073]
[4]
Jayson, G.C.; Kohn, E.C.; Kitchener, H.C.; Ledermann, J.A. Ovarian cancer. Lancet, 2014, 384(9951), 1376-1388.
[http://dx.doi.org/10.1016/S0140-6736(13)62146-7] [PMID: 24767708]
[5]
Agarwal, R.; Kaye, S.B. Ovarian cancer: Strategies for overcoming resistance to chemotherapy. Nat. Rev. Cancer, 2003, 3(7), 502-516.
[http://dx.doi.org/10.1038/nrc1123] [PMID: 12835670]
[6]
Harrigan, J.A.; Jacq, X.; Martin, N.M.; Jackson, S.P. Deubiquitylating enzymes and drug discovery: emerging opportunities. Nat. Rev. Drug Discov., 2018, 17(1), 57-78.
[http://dx.doi.org/10.1038/nrd.2017.152] [PMID: 28959952]
[7]
Abdul Rehman, S.A.; Kristariyanto, Y.A.; Choi, S.Y.; Nkosi, P.J.; Weidlich, S.; Labib, K.; Hofmann, K.; Kulathu, Y. mindy-1 is a member of an evolutionarily conserved and structurally distinct new family of deubiquitinating enzymes. Mol. Cell, 2016, 63(1), 146-155.
[http://dx.doi.org/10.1016/j.molcel.2016.05.009] [PMID: 27292798]
[8]
Wu, X.; Luo, Q.; Zhao, P.; Chang, W.; Wang, Y.; Shu, T.; Ding, F.; Li, B.; Liu, Z. JOSD1 inhibits mitochondrial apoptotic signalling to drive acquired chemoresistance in gynaecological cancer by stabilizing MCL1. Cell Death Differ., 2020, 27(1), 55-70.
[http://dx.doi.org/10.1038/s41418-019-0339-0] [PMID: 31043700]
[9]
Wu, X.; Luo, Q.; Zhao, P.; Chang, W.; Wang, Y.; Shu, T.; Ding, F.; Li, B.; Liu, Z. MGMT-activated DUB3 stabilizes MCL1 and drives chemoresistance in ovarian cancer. Proc. Natl. Acad. Sci. USA, 2019, 116(8), 2961-2966.
[http://dx.doi.org/10.1073/pnas.1814742116] [PMID: 30718431]
[10]
Velimezi, G.; Robinson-Garcia, L.; Muñoz-Martínez, F.; Wiegant, W.W.; Ferreira da Silva, J.; Owusu, M.; Moder, M.; Wiedner, M.; Rosenthal, S.B.; Fisch, K.M.; Moffat, J.; Menche, J.; van Attikum, H.; Jackson, S.P.; Loizou, J.I. Map of synthetic rescue interactions for the Fanconi anemia DNA repair pathway identifies USP48. Nat. Commun., 2018, 9(1), 2280.
[http://dx.doi.org/10.1038/s41467-018-04649-z] [PMID: 29891926]
[11]
Ye, S.; Lawlor, M.A.; Rivera-Reyes, A.; Egolf, S.; Chor, S.; Pak, K.; Ciotti, G.E.; Lee, A.C.; Marino, G.E.; Shah, J.; Niedzwicki, D.; Weber, K.; Park, P.M.C.; Alam, M.Z.; Grazioli, A.; Haldar, M.; Xu, M.; Perry, J.A.; Qi, J.; Eisinger-Mathason, T.S.K. YAP1-mediated suppression of USP31 enhances NFκB activity to promote sarcomagenesis. Cancer Res., 2018, 78(10), 2705-2720.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-4052] [PMID: 29490948]
[12]
Allemani, C.; Matsuda, T.; Di Carlo, V.; Harewood, R.; Matz, M.; Nikšić, M.; Bonaventure, A.; Valkov, M.; Johnson, C.J.; Estève, J.; Ogunbiyi, O.J.; Azevedo, E. Silva, G.; Chen, W.Q.; Eser, S.; Engholm, G.; Stiller, C.A.; Monnereau, A.; Woods, R.R.; Visser, O.; Lim, G.H.; Aitken, J.; Weir, H.K.; Coleman, M.P. CONCORD Working Group. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet, 2018, 391(10125), 1023-1075.
[http://dx.doi.org/10.1016/S0140-6736(17)33326-3] [PMID: 29395269]
[13]
Zhao, J. Cancer stem cells and chemoresistance: The smartest survives the raid. Pharmacol. Ther., 2016, 160, 145-158.
[http://dx.doi.org/10.1016/j.pharmthera.2016.02.008] [PMID: 26899500]
[14]
Lopez, J.; Banerjee, S.; Kaye, S.B. New developments in the treatment of ovarian cancer-future perspectives. Ann. Oncol., 2013, 24(Suppl. 10), x69-x76.
[http://dx.doi.org/10.1093/annonc/mdt475] [PMID: 24265409]
[15]
Patel, A.G.; Sarkaria, J.N.; Kaufmann, S.H. Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells. Proc. Natl. Acad. Sci. USA, 2011, 108(8), 3406-3411.
[http://dx.doi.org/10.1073/pnas.1013715108] [PMID: 21300883]
[16]
Ledermann, J.; Harter, P.; Gourley, C.; Friedlander, M.; Vergote, I.; Rustin, G.; Scott, C.; Meier, W.; Shapira-Frommer, R.; Safra, T.; Matei, D.; Macpherson, E.; Watkins, C.; Carmichael, J.; Matulonis, U. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N. Engl. J. Med., 2012, 366(15), 1382-1392.
[http://dx.doi.org/10.1056/NEJMoa1105535] [PMID: 22452356]
[17]
Bell, D.; Berchuck, A.; Birrer, M. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature, 2011, 474(7353), 609-615.
[http://dx.doi.org/10.1038/nature10166]] [PMID: 21720365]
[18]
Bolton, K.L.; Chenevix-Trench, G.; Goh, C.; Sadetzki, S.; Ramus, S.J.; Karlan, B.Y.; Lambrechts, D.; Despierre, E.; Barrowdale, D.; McGuffog, L.; Healey, S.; Easton, D.F.; Sinilnikova, O.; Benítez, J.; García, M.J.; Neuhausen, S.; Gail, M.H.; Hartge, P.; Peock, S.; Frost, D.; Evans, D.G.; Eeles, R.; Godwin, A.K.; Daly, M.B.; Kwong, A.; Ma, E.S.; Lázaro, C.; Blanco, I.; Montagna, M.; D’Andrea, E.; Nicoletto, M.O.; Johnatty, S.E.; Kjær, S.K.; Jensen, A.; Høgdall, E.; Goode, E.L.; Fridley, B.L.; Loud, J.T.; Greene, M.H.; Mai, P.L.; Chetrit, A.; Lubin, F.; Hirsh-Yechezkel, G.; Glendon, G.; Andrulis, I.L.; Toland, A.E.; Senter, L.; Gore, M.E.; Gourley, C.; Michie, C.O.; Song, H.; Tyrer, J.; Whittemore, A.S.; McGuire, V.; Sieh, W.; Kristoffersson, U.; Olsson, H.; Borg, Å.; Levine, D.A.; Steele, L.; Beattie, M.S.; Chan, S.; Nussbaum, R.L.; Moysich, K.B.; Gross, J.; Cass, I.; Walsh, C.; Li, A.J.; Leuchter, R.; Gordon, O.; Garcia-Closas, M.; Gayther, S.A.; Chanock, S.J.; Antoniou, A.C.; Pharoah, P.D. EMBRACE; kConFab Investigators; Cancer Genome Atlas Research Network. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA, 2012, 307(4), 382-390.
[http://dx.doi.org/10.1001/jama.2012.20] [PMID: 22274685]
[19]
McLachlan, J.; George, A.; Banerjee, S. The current status of PARP inhibitors in ovarian cancer. Tumori, 2016, 102(5), 433-440.
[http://dx.doi.org/10.5301/tj.5000558] [PMID: 27716873]
[20]
Coleman, R.L.; Oza, A.M.; Lorusso, D.; Aghajanian, C.; Oaknin, A.; Dean, A.; Colombo, N.; Weberpals, J.I.; Clamp, A.; Scambia, G.; Leary, A.; Holloway, R.W.; Gancedo, M.A.; Fong, P.C.; Goh, J.C.; O’Malley, D.M.; Armstrong, D.K.; Garcia-Donas, J.; Swisher, E.M.; Floquet, A.; Konecny, G.E.; McNeish, I.A.; Scott, C.L.; Cameron, T.; Maloney, L.; Isaacson, J.; Goble, S.; Grace, C.; Harding, T.C.; Raponi, M.; Sun, J.; Lin, K.K.; Giordano, H.; Ledermann, J.A. ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2017, 390(10106), 1949-1961.
[http://dx.doi.org/10.1016/S0140-6736(17)32440-6] [PMID: 28916367]
[21]
Moore, K.; Colombo, N.; Scambia, G.; Kim, B.G.; Oaknin, A.; Friedlander, M.; Lisyanskaya, A.; Floquet, A.; Leary, A.; Sonke, G.S.; Gourley, C.; Banerjee, S.; Oza, A.; González-Martín, A.; Aghajanian, C.; Bradley, W.; Mathews, C.; Liu, J.; Lowe, E.S.; Bloomfield, R.; DiSilvestro, P. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N. Engl. J. Med., 2018, 379(26), 2495-2505.
[http://dx.doi.org/10.1056/NEJMoa1810858] [PMID: 30345884]
[22]
Lambert, A.W.; Pattabiraman, D.R.; Weinberg, R.A. Emerging biological principles of metastasis. Cell, 2017, 168(4), 670-691.
[http://dx.doi.org/10.1016/j.cell.2016.11.037] [PMID: 28187288]
[23]
Nieto, M.A.; Huang, R.Y.; Jackson, R.A.; Thiery, J.P. EMT: 2016. Cell, 2016, 166(1), 21-45.
[http://dx.doi.org/10.1016/j.cell.2016.06.028] [PMID: 27368099]
[24]
Chung, J.H.; Rho, J.K.; Xu, X.; Lee, J.S.; Yoon, H.I.; Lee, C.T.; Choi, Y.J.; Kim, H-R.; Kim, C.H.; Lee, J.C. Clinical and molecular evidences of epithelial to mesenchymal transition in acquired resistance to EGFR-TKIs. Lung Cancer, 2011, 73(2), 176-182.
[http://dx.doi.org/10.1016/j.lungcan.2010.11.011] [PMID: 21168239]
[25]
Shang, Y.; Cai, X.; Fan, D. Roles of epithelial-mesenchymal transition in cancer drug resistance. Curr. Cancer Drug Targets, 2013, 13(9), 915-929.
[http://dx.doi.org/10.2174/15680096113136660097] [PMID: 24168191]
[26]
Lin, Z. L.; Sun, S.; Xie, S.; Zhang, S.; Fan, Q.; Li, W.; Chen, G.; Pan, W.; Wang, B.; Weng, Z.; Zhang, B.; Liu, J. Chemotherapy-induced long non-coding RNA 1 promotes metastasis and chemo-resistance of TSCC via the Wnt/beta-catenin signaling pathway. Mol. Ther., 2018, 26(6), 1494-1508.
[http://dx.doi.org/10.1016/j.ymthe.2018.04.002] [PMID: 29699939]
[27]
Sesumi, Y.; Suda, K.; Mizuuchi, H.; Kobayashi, Y.; Sato, K.; Chiba, M.; Shimoji, M.; Tomizawa, K.; Takemoto, T.; Mitsudomi, T. Effect of dasatinib on EMT-mediated-mechanism of resistance against EGFR inhibitors in lung cancer cells. Lung Cancer, 2017, 104, 85-90.
[http://dx.doi.org/10.1016/j.lungcan.2016.12.012] [PMID: 28213007]
[28]
Luise, C.; Capra, M.; Donzelli, M.; Mazzarol, G.; Jodice, M.G.; Nuciforo, P.; Viale, G.; Di Fiore, P.P.; Confalonieri, S. An atlas of altered expression of deubiquitinating enzymes in human cancer. PLoS One, 2011, 6(1) e15891
[http://dx.doi.org/10.1371/journal.pone.0015891] [PMID: 21283576]
[29]
Du, T.; Li, H.; Fan, Y.; Yuan, L.; Guo, X.; Zhu, Q.; Yao, Y.; Li, X.; Liu, C.; Yu, X.; Liu, Z.; Cui, C.P.; Han, C.; Zhang, L. The deubiquitylase OTUD3 stabilizes GRP78 and promotes lung tumorigenesis. Nat. Commun., 2019, 10(1), 2914.
[http://dx.doi.org/10.1038/s41467-019-10824-7] [PMID: 31266968]
[30]
Zhang, J.; Zhang, P.; Wei, Y.; Piao, H.L.; Wang, W.; Maddika, S.; Wang, M.; Chen, D.; Sun, Y.; Hung, M.C.; Chen, J.; Ma, L. Deubiquitylation and stabilization of PTEN by USP13. Nat. Cell Biol., 2013, 15(12), 1486-1494.
[http://dx.doi.org/10.1038/ncb2874] [PMID: 24270891]
[31]
Diefenbacher, M.E.; Popov, N.; Blake, S.M.; Schülein-Völk, C.; Nye, E.; Spencer-Dene, B.; Jaenicke, L.A.; Eilers, M.; Behrens, A. The deubiquitinase USP28 controls intestinal homeostasis and promotes colorectal cancer. J. Clin. Invest., 2014, 124(8), 3407-3418.
[http://dx.doi.org/10.1172/JCI73733] [PMID: 24960159]
[32]
Zhou, A.; Lin, K.; Zhang, S.; Ma, L.; Xue, J.; Morris, S.A.; Aldape, K.D.; Huang, S. Gli1-induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1. EMBO Rep., 2017, 18(8), 1318-1330.
[http://dx.doi.org/10.15252/embr.201643124] [PMID: 28623188]
[33]
Cetkovská, K.; Šustová, H.; Uldrijan, S. Ubiquitin-specific peptidase 48 regulates Mdm2 protein levels independent of its deubiquitinase activity. Sci. Rep., 2017, 7, 43180.
[http://dx.doi.org/10.1038/srep43180] [PMID: 28233861]
[34]
Shu, T.; Li, Y.; Wu, X.; Li, B.; Liu, Z. Down-regulation of HECTD3 by HER2 inhibition makes serous ovarian cancer cells sensitive to platinum treatment. Cancer Lett., 2017, 411, 65-73.
[http://dx.doi.org/10.1016/j.canlet.2017.09.048] [PMID: 28989055]

Rights & Permissions Print Cite
Article Metrics
69
1
© 2024 Bentham Science Publishers | Privacy Policy