TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation

References

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–16. doi:10.3322/caac.21660.
   PubMed Web of Science ®Google Scholar
• Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48. doi:10.3322/caac.21763.
   PubMed Web of Science ®Google Scholar
• Yousefi M, Dehghani S, Nosrati R, Ghanei M, Salmaninejad A, Rajaie S, Hasanzadeh M, Pasdar A. Current insights into the metastasis of epithelial ovarian cancer - hopes and hurdles. Cell Oncol (Dordr). 2020;43(4):515–538. doi:10.1007/s13402-020-00513-9.
   PubMed Web of Science ®Google Scholar
• Kuroki L, Guntupalli SR. Treatment of epithelial ovarian cancer. BMJ. 2020;371:m3773. doi:10.1136/bmj.m3773.
   PubMed Web of Science ®Google Scholar
• Lheureux S, Gourley C, Vergote I, Oza AM. Epithelial ovarian cancer. Lancet. 2019;393(10177):1240–1253. doi:10.1016/s0140-6736(18)32552-2.
   PubMed Web of Science ®Google Scholar
• Markman M, Blessing J, Rubin SC, Connor J, Hanjani P, Waggoner S. Phase ii trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a gynecologic oncology group study. Gynecol Oncol. 2006;101(3):436–440. doi:10.1016/j.ygyno.2005.10.036.
   PubMed Web of Science ®Google Scholar
• Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, Wang Y, Scribner DR Jr., Marciniack M, Naumann RW, et al. Randomized phase iii trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007;25(19):2811–2818. doi:10.1200/jco.2006.09.6735.
   PubMed Web of Science ®Google Scholar
• du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I, Pfisterer J. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the arbeitsgemeinschaft gynaekologische onkologie studiengruppe ovarialkarzinom (ago-ovar) and the groupe d’investigateurs nationaux pour les etudes des cancers de l’ovaire (gineco). Cancer. 2009;115(6):1234–1244. doi:10.1002/cncr.24149.
   PubMed Web of Science ®Google Scholar
• Rose PG, Blessing JA, Mayer AR, Homesley HD. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a gynecologic oncology group study. J Clin Oncol. 1998;16(2):405–410. doi:10.1200/jco.1998.16.2.405.
   PubMed Web of Science ®Google Scholar
• Lan CY, Wang Y, Xiong Y, Li JD, Shen JX, Li YF, Zheng M, Zhang YN, Feng YL, Liu Q, et al. Apatinib combined with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer (aeroc): a phase 2, single-arm, prospective study. Lancet Oncol. 2018;19(9):1239–1246. doi:10.1016/s1470-2045(18)30349-8.
   PubMed Web of Science ®Google Scholar
• Huang Q, Chu C, Tang J, Dai Z. Efficacy and safety of apatinib combined with etoposide in patients with recurrent platinum-resistant epithelial ovarian cancer: a retrospective study. J Cancer. 2020;11(18):5353–5358. doi:10.7150/jca.45547.
   PubMed Web of Science ®Google Scholar
• Bush NG, Evans-Roberts K, Maxwell A, Lovett ST. DNA topoisomerases. EcoSal Plus. 2015;6(2). doi:10.1128/ecosalplus.ESP-0010-2014.
   PubMedGoogle Scholar
• Tarpgaard LS, Qvortrup C, Nygård SB, Nielsen SL, Andersen DR, Jensen NF, Stenvang J, Detlefsen S, Brünner N, Pfeiffer P. A phase ii study of epirubicin in oxaliplatin-resistant patients with metastatic colorectal cancer and top2a gene amplification. BMC Cancer. 2016;16(91):1–5. doi:10.1186/s12885-016-2124-5.
   Google Scholar
• Ma Y, North BJ, Shu J. Regulation of topoisomerase ii stability and activity by ubiquitination and sumoylation: clinical implications for cancer chemotherapy. Mol Biol Rep. 2021;48(9):6589–6601. doi:10.1007/s11033-021-06665-7.
   PubMed Web of Science ®Google Scholar
• Chen T, Sun Y, Ji P, Kopetz S, Zhang W. Topoisomerase iiα in chromosome instability and personalized cancer therapy. Oncogene. 2015;34(31):4019–4031. doi:10.1038/onc.2014.332.
   PubMed Web of Science ®Google Scholar
• Uusküla-Reimand L, Wilson MD. Untangling the roles of top2a and top2b in transcription and cancer. Sci Adv. 2022;8(44):eadd4920. doi:10.1126/sciadv.add4920.
   PubMed Web of Science ®Google Scholar
• Zhang R, Xu J, Zhao J, Bai JH. Proliferation and invasion of colon cancer cells are suppressed by knockdown of top2a. J Cell Biochem. 2018;119(9):7256–7263. doi:10.1002/jcb.26916.
   PubMed Web of Science ®Google Scholar
• Dong Y, Sun X, Zhang K, He X, Zhang Q, Song H, Xu M, Lu H, Ren R. Type iia topoisomerase (top2a) triggers epithelial-mesenchymal transition and facilitates hcc progression by regulating snail expression. Bioengineered. 2021;12(2):12967–12979. doi:10.1080/21655979.2021.2012069.
   PubMed Web of Science ®Google Scholar
• Scott AT, Weitz M, Breheny PJ, Ear PH, Darbro B, Brown BJ, Braun TA, Li G, Umesalma S, Kaemmer CA, et al. Gene expression signatures identify novel therapeutics for metastatic pancreatic neuroendocrine tumors. Clin Cancer Res. 2020;26(8):2011–2021. doi:10.1158/1078-0432.Ccr-19-2884.
   PubMed Web of Science ®Google Scholar
• Labbé DP, Sweeney CJ, Brown M, Galbo P, Rosario S, Wadosky KM, Ku SY, Sjöström M, Alshalalfa M, Erho N, et al. Top2a and ezh2 provide early detection of an aggressive prostate cancer subgroup. Clin Cancer Res. 2017;23(22):7072–7083. doi:10.1158/1078-0432.Ccr-17-0413.
   PubMed Web of Science ®Google Scholar
• Hou GX, Liu P, Yang J, Wen S. Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using oncomine and Kaplan-Meier plotter. PLoS One. 2017;12(3):e0174515. doi:10.1371/journal.pone.0174515.
   PubMed Web of Science ®Google Scholar
• Yu B, Chen L, Zhang W, Li Y, Zhang Y, Gao Y, Teng X, Zou L, Wang Q, Jia H, et al. Top2a and cenpf are synergistic master regulators activated in cervical cancer. BMC Med Genomics. 2020;13(1):145. doi:10.1186/s12920-020-00800-2.
   PubMed Web of Science ®Google Scholar
• Erriquez J, Becco P, Olivero M, Ponzone R, Maggiorotto F, Ferrero A, Scalzo MS, Canuto EM, Sapino A, Verdun di Cantogno L, et al. Top2a gene copy gain predicts response of epithelial ovarian cancers to pegylated liposomal doxorubicin: Top2a as marker of response to pld in ovarian cancer. Gynecol Oncol. 2015;138(3):627–633. doi:10.1016/j.ygyno.2015.06.025.
   PubMed Web of Science ®Google Scholar
• Ghisoni E, Maggiorotto F, Borella F, Mittica G, Genta S, Giannone G, Katsaros D, Sciarrillo A, Ferrero A, Sarotto I, et al. Top2a as marker of response to pegylated lyposomal doxorubicin (pld) in epithelial ovarian cancers. J Ovarian Res. 2019;12(1):17. doi:10.1186/s13048-019-0492-6.
   PubMedGoogle Scholar
• Bai Y, Li LD, Li J, Lu X. Targeting of topoisomerases for prognosis and drug resistance in ovarian cancer. J Ovarian Res. 2016;9(1):35. doi:10.1186/s13048-016-0244-9.
   PubMedGoogle Scholar
• Nitulescu GM, Van De Venter M, Nitulescu G, Ungurianu A, Juzenas P, Peng Q, Olaru OT, Grădinaru D, Tsatsakis A, Tsoukalas D, et al. The akt pathway in oncology therapy and beyond (review). Int J Oncol. 2018;53(6):2319–2331. doi:10.3892/ijo.2018.4597.
   PubMed Web of Science ®Google Scholar
• Alzahrani AS. Pi3k/Akt/Mtor inhibitors in cancer: At the bench and bedside. Semin Cancer Biol. 2019;59:125–132. doi:10.1016/j.semcancer.2019.07.009.
   PubMed Web of Science ®Google Scholar
• Li H, Prever L, Hirsch E, Gulluni F. Targeting pi3k/akt/mtor signaling pathway in breast cancer. Cancers Basel. 2021;13(14):3517. doi:10.3390/cancers13143517.
   PubMed Web of Science ®Google Scholar
• Hao Y, Samuels Y, Li Q, Krokowski D, Guan BJ, Wang C, Jin Z, Dong B, Cao B, Feng X, et al. Oncogenic pik3ca mutations reprogram glutamine metabolism in colorectal cancer. Nat Commun. 2016;7(1):11971. doi:10.1038/ncomms11971.
   PubMedGoogle Scholar
• Ediriweera MK, Tennekoon KH, Samarakoon SR. Role of the pi3k/akt/mtor signaling pathway in ovarian cancer: biological and therapeutic significance. Semin Cancer Biol. 2019;59:147–160. doi:10.1016/j.semcancer.2019.05.012.
   PubMed Web of Science ®Google Scholar
• Lyu WJ, Shu YJ, Liu YB, Dong P. Topoisomerase ii alpha promotes gallbladder cancer proliferation and metastasis through activating phosphatidylinositol 3-kinase/protein kinase b/mammalian target of rapamycin signaling pathway. Chin Med J (Engl). 2020;133(19):2321–2329. doi:10.1097/cm9.0000000000001075.
   PubMed Web of Science ®Google Scholar
• Ozols RF. Oral etoposide for the treatment of recurrent ovarian cancer. Drugs. 1999;Suppl 58(Supplement 3):43–49. doi:10.2165/00003495-199958003-00007.
   Google Scholar
• Zhang J, Bajari R, Andric D, Gerthoffert F, Lepsa A, Nahal-Bose H, Stein LD, Ferretti V. The international cancer genome consortium data portal. Nat Biotechnol. 2019;37(4):367–369. doi:10.1038/s41587-019-0055-9.
   PubMed Web of Science ®Google Scholar
• Doll KM, Rademaker A, Sosa JA. Practical guide to surgical data sets: surveillance, epidemiology, and end results (seer) database. JAMA Surg. 2018;153(6):588–589. doi:10.1001/jamasurg.2018.0501.
   PubMed Web of Science ®Google Scholar
• Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, et al. NCBI GEO: archive for functional genomics data sets—update. Nucleic Acids Res. 2013;41(D1):D991–995. doi:10.1093/nar/gks1193.
   PubMed Web of Science ®Google Scholar
• Liu T, Zhang H, Yi S, Gu L, Zhou M. Mutual regulation of mdm4 and top2a in cancer cell proliferation. Mol Oncol. 2019;13(5):1047–1058. doi:10.1002/1878-0261.12457.
   PubMed Web of Science ®Google Scholar
• Cui Y, Pu R, Ye J, Huang H, Liao D, Yang Y, Chen W, Yao Y, He Y. Lncrna fam230b promotes gastric cancer growth and metastasis by regulating the mir-27a-5p/top2a axis. Dig Dis Sci. 2021;66(8):2637–2650. doi:10.1007/s10620-020-06581-z.
   PubMed Web of Science ®Google Scholar
• Albero R, Enjuanes A, Demajo S, Castellano G, Pinyol M, García N, Capdevila C, Clot G, Suárez-Cisneros H, Shimada M, et al. Cyclin d1 overexpression induces global transcriptional downregulation in lymphoid neoplasms. J Clin Invest. 2018;128(9):4132–4147. doi:10.1172/jci96520.
   PubMed Web of Science ®Google Scholar
• Dozier C, Mazzolini L, Cénac C, Froment C, Burlet-Schiltz O, Besson A, Manenti S. Cyclind-cdk4/6 complexes phosphorylate cdc25a and regulate its stability. Oncogene. 2017;36(26):3781–3788. doi:10.1038/onc.2016.506.
   PubMed Web of Science ®Google Scholar
• Ding J, Xu K, Sun S, Qian C, Yin S, Xie H, Zhou L, Zheng S, Zhang W. Socs1 blocks g1-s transition in hepatocellular carcinoma by reducing the stability of the cyclind1/cdk4 complex in the nucleus. Aging (Albany NY). 2020;12(4):3962–3975. doi:10.18632/aging.102865.
   PubMedGoogle Scholar
• Feng Z, Xia Y, Gao T, Xu F, Lei Q, Peng C, Yang Y, Xue Q, Hu X, Wang Q, et al. The antipsychotic agent trifluoperazine hydrochloride suppresses triple-negative breast cancer tumor growth and brain metastasis by inducing g0/g1 arrest and apoptosis. Cell Death Disease. 2018;9(10):1006. doi:10.1038/s41419-018-1046-3.
   PubMedGoogle Scholar
• Wu P, Meng X, Zheng H, Zeng Q, Chen T, Wang W, Zhang X, Su J. Kaempferol attenuates ros-induced hemolysis and the molecular mechanism of its induction of apoptosis on bladder cancer. Molecules. 2018;23(10):2592. doi:10.3390/molecules23102592.
   PubMed Web of Science ®Google Scholar
• Meng X, Ma J, Wang B, Wu X, Liu Z. Long non-coding RNA oip5-as1 promotes pancreatic cancer cell growth through sponging mir-342-3p via akt/erk signaling pathway. J Physiol Biochem. 2020;76(2):301–315. doi:10.1007/s13105-020-00734-4.
   PubMed Web of Science ®Google Scholar
• Duan PJ, Zhao JH, Xie LL. Cul4b promotes the progression of ovarian cancer by upregulating the expression of cdk2 and cyclind1. J Ovarian Res. 2020;13(1):76. doi:10.1186/s13048-020-00677-w.
   PubMed Web of Science ®Google Scholar
• Liu X, Zuo X, Sun X, Tian X, Teng Y. Hexokinase 2 promotes cell proliferation and tumor formation through the wnt/β-catenin pathway-mediated cyclin d1/c-myc upregulation in epithelial ovarian cancer. J Cancer. 2022;13(8):2559–2569. doi:10.7150/jca.71894.
   PubMed Web of Science ®Google Scholar
• Georgakilas AG, Martin OA, Bonner WM. p21: a two-faced genome guardian. Trends Mol Med. 2017;2323(4):310–319. doi:10.1016/j.molmed.2017.02.001.
   PubMed Web of Science ®Google Scholar
• Dhanasekaran R, Deutzmann A, Mahauad-Fernandez WD, Hansen AS, Gouw AM, Felsher DW. The myc oncogene - the grand orchestrator of cancer growth and immune evasion. Nat Rev Clin Oncol. 2022;19(1):23–36. doi:10.1038/s41571-021-00549-2.
   PubMed Web of Science ®Google Scholar
• Lv M, Xu Q, Zhang B, Yang Z, Xie J, Guo J, He F, Wang W. Imperatorin induces autophagy and g0/g1 phase arrest via PTEN-PI3K-AKT-mTOR/p21 signaling pathway in human osteosarcoma cells in vitro and in vivo. Cancer Cell Int. 2021;21(1):689. doi:10.1186/s12935-021-02397-7.
   PubMed Web of Science ®Google Scholar
• Gasparri ML, Bardhi E, Ruscito I, Papadia A, Farooqi AA, Marchetti C, Bogani G, Ceccacci I, Mueller MD, Benedetti Panici P. Pi3k/Akt/Mtor pathway in ovarian cancer treatment: are we on the right track? Geburtshilfe Frauenheilkd. 2017;77(10):1095–1103. doi:10.1055/s-0043-118907.
   PubMed Web of Science ®Google Scholar
• Yu H, Chen L, Wang X, Tang F, Wan Z, Wang H, Fu Q, Chen Z, Shi J, Hu X, et al. STIL promotes tumorigenesis of bladder cancer by activating PI3K/AKT/mTOR signaling pathway and targeting c-myc. Cancers Basel. 2022;14(23):5777. doi:10.3390/cancers14235777.
   PubMed Web of Science ®Google Scholar
• Fan X, He Y, Wu G, Chen H, Cheng X, Zhan Y, An C, Chen T, Wang X. Sirt3 activates autophagy to prevent dox-induced senescence by inactivating pi3k/akt/mtor pathway in a549 cells. Biochim Biophys Acta Mol Cell Res. 2023;1870(2):119411. doi:10.1016/j.bbamcr.2022.119411.
   PubMed Web of Science ®Google Scholar
• Withoff S, van der Zee AG, de Jong S, Hollema H, Smit EF, Mulder NH, de Vries EG. DNA topoisomerase iialpha and -beta expression in human ovarian cancer. Br J Cancer. 1999;79(5–6):748–753. doi:10.1038/sj.bjc.6690120.
   PubMed Web of Science ®Google Scholar
• Faggad A, Darb-Esfahani S, Wirtz R, Sinn B, Sehouli J, Könsgen D, Lage H, Weichert W, Noske A, Budczies J, et al. Topoisomerase iialpha mRNA and protein expression in ovarian carcinoma: correlation with clinicopathological factors and prognosis. Mod Pathol. 2009;22(4):579–588. doi:10.1038/modpathol.2009.14.
   PubMed Web of Science ®Google Scholar
• Perez-Fidalgo JA, Cortés A, Guerra E, García Y, Iglesias M, Bohn Sarmiento U, Calvo García E, Manso Sánchez L, Santaballa A, Oaknin A, et al. Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a geico phase ii trial (rolando study). ESMO Open. 2021;6(4):100212. doi:10.1016/j.esmoop.2021.100212.
   PubMed Web of Science ®Google Scholar
• Lánczky A, Győrffy B. Web-based survival analysis tool tailored for medical research (kmplot): development and implementation. J Med Internet Res. 2021;23(7):e27633. doi:10.2196/27633.
   PubMed Web of Science ®Google Scholar
• Tang Z, Kang B, Li C, Chen T, Zhang Z. Gepia2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47(W1):W556–w560. doi:10.1093/nar/gkz430.
   PubMed Web of Science ®Google Scholar
• Nusinow DP, Szpyt J, Ghandi M, Rose CM, McDonald ER 3rd, Kalocsay M, Jané-Valbuena J, Gelfand E, Schweppe DK, Jedrychowski M, et al. Quantitative proteomics of the cancer cell line encyclopedia. Cell. 2020;180(2):387–402.e316. doi:10.1016/j.cell.2019.12.023.
   PubMed Web of Science ®Google Scholar
• Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mrnas. Elife. 2015;4:e05005. doi:10.7554/eLife.05005.
   PubMed Web of Science ®Google Scholar
• Tian W, Zhu Y, Wang Y, Teng F, Zhang H, Liu G, Ma X, Sun D, Rohan T, Xue F. Visfatin, a potential biomarker and prognostic factor for endometrial cancer. Gynecol Oncol. 2013;129(3):505–512. doi:10.1016/j.ygyno.2013.02.022.
   PubMed Web of Science ®Google Scholar