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当代肿瘤药物靶点

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

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Research Article

PBX1 参与雌激素介导的膀胱癌进展和影响雌激素受体的化学抗性

卷 22, 期 9, 2022

发表于: 28 June, 2022

页: [757 - 770] 页: 14

弟呕挨: 10.2174/1568009622666220413084456

价格: $65

摘要

背景：膀胱癌（BCa）是一种常见的癌症，在全球范围内具有高发病率和高死亡率。据报道，前 B 细胞白血病转录因子 1 (PBX1) 与肿瘤进展有关。 目的：本研究的目的是探讨 PBX1 在 BCa 中的具体作用及其潜在机制。 方法：通过RT-qPCR和蛋白质印迹分析PBX1在肌肉侵袭性BCa组织和细胞系中的相对表达。 Kaplan-Meier 分析用于分析 PBX1 水平与生存状态之间的关系。采用共免疫沉淀 (CO-IP) 和染色质免疫沉淀 (ChIP)-qPCR 测定验证 PBX1 与雌激素受体 (ER) 之间的相互作用，并探索雌激素受体 (ER) 依赖性基因转录。 结果：PBX1在侵袭性BCa患者和BCa细胞中上调，与肿瘤大小、淋巴结转移、远处转移和较差的生存状态呈正相关。 PBX1的过表达促进BCa细胞的细胞生长、侵袭、上皮-间质转化（EMT）过程和顺铂耐药，而PBX1的沉默则表现出相反的作用。此外，PBX1 与 ER 相互作用，是 ER 功能所必需的。 PBX1过表达加重了雌激素对BCa细胞的促肿瘤作用，而部分抑制了ER拮抗剂AZD9496对BCa细胞的抑制作用。 结论：本研究表明，PBX1 通过结合和激活雌激素受体参与雌激素介导的 BCa 进展和化疗耐药。因此，PBX1 可作为 BCa 治疗的潜在预后和治疗靶点。

关键词: 膀胱癌、PBX1、雌激素受体、化疗耐药性、发病率、死亡率。

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[1]
Sanli, O.; Dobruch, J.; Knowles, M.A.; Burger, M.; Alemozaffar, M.; Nielsen, M.E.; Lotan, Y. Bladder cancer. Nat. Rev. Dis. Primers, 2017, 3(1), 17022.
[http://dx.doi.org/10.1038/nrdp.2017.22] [PMID: 28406148]
[2]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[3]
Dy, G.W.; Gore, J.L.; Forouzanfar, M.H.; Naghavi, M.; Fitzmaurice, C. Global burden of urologic cancers, 1990–2013. Eur. Urol., 2017, 71(3), 437-446.
[http://dx.doi.org/10.1016/j.eururo.2016.10.008] [PMID: 28029399]
[4]
Soloway, M.S. Bladder cancer: Lack of progress in bladder cancer--what are the obstacles? Nat. Rev. Urol., 2013, 10(1), 5-6.
[http://dx.doi.org/10.1038/nrurol.2012.219] [PMID: 23165404]
[5]
Ferraz-de-Souza, B.; Martin, F.; Mallet, D.; Hudson-Davies, R.E.; Cogram, P.; Lin, L.; Gerrelli, D.; Beuschlein, F.; Morel, Y.; Huebner, A.; Achermann, J.C. CBP/p300-interacting transactivator, with Glu/Asp-rich C-terminal domain, 2, and pre-B-cell leukemia transcription factor 1 in human adrenal development and disease. J. Clin. Endocrinol. Metab., 2009, 94(2), 678-683.
[http://dx.doi.org/10.1210/jc.2008-1064] [PMID: 18984668]
[6]
Schnabel, C.A.; Selleri, L.; Cleary, M.L. Pbx1 is essential for adrenal development and urogenital differentiation. Genesis, 2003, 37(3), 123-130.
[http://dx.doi.org/10.1002/gene.10235] [PMID: 14595835]
[7]
Teoh, P.H.; Shu-Chien, A.C.; Chan, W.K. Pbx1 is essential for growth of zebrafish swim bladder. Dev. Dyn., 2010, 239(3), 865-874.
[http://dx.doi.org/10.1002/dvdy.22221] [PMID: 20108353]
[8]
Kamps, M.P.; Look, A.T.; Baltimore, D. The human t(1;19) translocation in pre-B ALL produces multiple nuclear E2A-Pbx1 fusion proteins with differing transforming potentials. Genes Dev., 1991, 5(3), 358-368.
[http://dx.doi.org/10.1101/gad.5.3.358] [PMID: 1672117]
[9]
Jung, J-G.; Shih, I-M.; Park, J.T.; Gerry, E.; Kim, T.H.; Ayhan, A.; Handschuh, K.; Davidson, B.; Fader, A.N.; Selleri, L.; Wang, T.L. Ovarian cancer chemoresistance relies on the stem cell reprogramming factor PBX1. Cancer Res., 2016, 76(21), 6351-6361.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-0980] [PMID: 27590741]
[10]
Shiraishi, K.; Yamasaki, K.; Nanba, D.; Inoue, H.; Hanakawa, Y.; Shirakata, Y.; Hashimoto, K.; Higashiyama, S. Pre-B-cell leukemia transcription factor 1 is a major target of promyelocytic leukemia zinc-finger-mediated melanoma cell growth suppression. Oncogene, 2007, 26(3), 339-348.
[http://dx.doi.org/10.1038/sj.onc.1209800] [PMID: 16862184]
[11]
Okada, S.; Irié, T.; Tanaka, J.; Yasuhara, R.; Yamamoto, G.; Isobe, T.; Hokazono, C.; Tachikawa, T.; Kohno, Y.; Mishima, K. Potential role of hematopoietic pre-B-cell leukemia transcription factor-interacting protein in oral carcinogenesis. J. Oral Pathol. Med., 2015, 44(2), 115-125.
[http://dx.doi.org/10.1111/jop.12210] [PMID: 25060351]
[12]
Magnani, L.; Ballantyne, E.B.; Zhang, X.; Lupien, M. PBX1 genomic pioneer function drives ERα signaling underlying progression in breast cancer. PLoS Genet., 2011, 7(11), e1002368.
[http://dx.doi.org/10.1371/journal.pgen.1002368] [PMID: 22125492]
[13]
Kikugawa, T.; Kinugasa, Y.; Shiraishi, K.; Nanba, D.; Nakashiro, K.; Tanji, N.; Yokoyama, M.; Higashiyama, S. PLZF regulates Pbx1 transcription and Pbx1-HoxC8 complex leads to androgen-independent prostate cancer proliferation. Prostate, 2006, 66(10), 1092-1099.
[http://dx.doi.org/10.1002/pros.20443] [PMID: 16637071]
[14]
Wei, X.; Yu, L.; Li, Y. PBX1 promotes the cell proliferation via JAK2/STAT3 signaling in clear cell renal carcinoma. Biochem. Biophys. Res. Commun., 2018, 500(3), 650-657.
[http://dx.doi.org/10.1016/j.bbrc.2018.04.127] [PMID: 29678569]
[15]
Magnani, L.; Patten, D.K.; Nguyen, V.T.; Hong, S.P.; Steel, J.H.; Patel, N.; Lombardo, Y.; Faronato, M.; Gomes, A.R.; Woodley, L.; Page, K.; Guttery, D.; Primrose, L.; Fernandez Garcia, D.; Shaw, J.; Viola, P.; Green, A.; Nolan, C.; Ellis, I.O.; Rakha, E.A.; Shousha, S.; Lam, E.W. Győrffy, B.; Lupien, M.; Coombes, R.C. The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer. Oncotarget, 2015, 6(26), 21878-21891.
[http://dx.doi.org/10.18632/oncotarget.4243] [PMID: 26215677]
[16]
Le Tanno, P.; Breton, J.; Bidart, M.; Satre, V.; Harbuz, R.; Ray, P.F.; Bosson, C.; Dieterich, K.; Jaillard, S.; Odent, S.; Poke, G.; Beddow, R.; Digilio, M.C.; Novelli, A.; Bernardini, L.; Pisanti, M.A.; Mackenroth, L.; Hackmann, K.; Vogel, I.; Christensen, R.; Fokstuen, S.; Béna, F.; Amblard, F.; Devillard, F.; Vieville, G.; Apostolou, A.; Jouk, P.S.; Guebre-Egziabher, F.; Sartelet, H.; Coutton, C. PBX1 haploinsufficiency leads to syndromic congenital anomalies of the kidney and urinary tract (CAKUT) in humans. J. Med. Genet., 2017, 54(7), 502-510.
[http://dx.doi.org/10.1136/jmedgenet-2016-104435] [PMID: 28270404]
[17]
Dobruch, J.; Daneshmand, S.; Fisch, M.; Lotan, Y.; Noon, A.P.; Resnick, M.J.; Shariat, S.F.; Zlotta, A.R.; Boorjian, S.A. Gender and bladder cancer: A collaborative review of etiology, biology, and outcomes. Eur. Urol., 2016, 69(2), 300-310.
[http://dx.doi.org/10.1016/j.eururo.2015.08.037] [PMID: 26346676]
[18]
Kauffman, E.C.; Robinson, B.D.; Downes, M.; Marcinkiewicz, K.; Vourganti, S.; Scherr, D.S.; Gudas, L.J.; Mongan, N.P. Estrogen receptor-β expression and pharmacological targeting in bladder cancer. Oncol. Rep., 2013, 30(1), 131-138.
[http://dx.doi.org/10.3892/or.2013.2416] [PMID: 23612777]
[19]
Ou, Z.; Wang, Y.; Chen, J.; Tao, L.; Zuo, L.; Sahasrabudhe, D.; Joseph, J.; Wang, L.; Yeh, S. Estrogen receptor β promotes bladder cancer growth and invasion via alteration of miR-92a/DAB2IP signals. Exp. Mol. Med., 2018, 50(11), 1-11.
[http://dx.doi.org/10.1038/s12276-018-0155-5] [PMID: 30459405]
[20]
Goto, T.; Kashiwagi, E.; Jiang, G.; Nagata, Y.; Teramoto, Y.; Baras, A.S.; Yamashita, S.; Ito, A.; Arai, Y.; Miyamoto, H. Estrogen receptor-β signaling induces cisplatin resistance in bladder cancer. Am. J. Cancer Res., 2020, 10(8), 2523-2534.
[PMID: 32905529]
[21]
Toska, E.; Osmanbeyoglu, H.U.; Castel, P.; Chan, C.; Hendrickson, R.C.; Elkabets, M.; Dickler, M.N.; Scaltriti, M.; Leslie, C.S.; Armstrong, S.A.; Baselga, J. PI3K pathway regulates ER-dependent transcription in breast cancer through the epigenetic regulator KMT2D. Science, 2017, 355(6331), 1324-1330.
[http://dx.doi.org/10.1126/science.aah6893] [PMID: 28336670]
[22]
Toska, E.; Castel, P.; Chhangawala, S.; Arruabarrena-Aristorena, A.; Chan, C.; Hristidis, V.C.; Cocco, E.; Sallaku, M.; Xu, G.; Park, J.; Minuesa, G.; Shifman, S.G.; Socci, N.D.; Koche, R.; Leslie, C.S.; Scaltriti, M.; Baselga, J. PI3K inhibition activates SGK1 via a feedback loop to promote chromatin-based regulation of ER-dependent gene expression. Cell Rep., 2019, 27(1), 294-306.e5.
[http://dx.doi.org/10.1016/j.celrep.2019.02.111] [PMID: 30943409]
[23]
Ao, X.; Ding, W.; Ge, H.; Zhang, Y.; Ding, D.; Liu, Y. PBX1 is a valuable prognostic biomarker for patients with breast cancer. Exp. Ther. Med., 2020, 20(1), 385-394.
[http://dx.doi.org/10.3892/etm.2020.8705] [PMID: 32565927]
[24]
Hayashi, T.; Seiler, R.; Oo, H.Z.; Jäger, W.; Moskalev, I.; Awrey, S.; Dejima, T.; Todenhöfer, T.; Li, N.; Fazli, L.; Matsubara, A.; Black, P.C. Targeting HER2 with T-DM1, an antibody cytotoxic drug conjugate, is effective in HER2 over expressing bladder cancer. J. Urol., 2015, 194(4), 1120-1131.
[http://dx.doi.org/10.1016/j.juro.2015.05.087] [PMID: 26047983]
[25]
Chen, W.M.; Huang, M.D.; Sun, D.P.; Kong, R.; Xu, T.P.; Xia, R.; Zhang, E.B.; Shu, Y.Q. Long intergenic non-coding RNA 00152 promotes tumor cell cycle progression by binding to EZH2 and repressing p15 and p21 in gastric cancer. Oncotarget, 2016, 7(9), 9773-9787.
[http://dx.doi.org/10.18632/oncotarget.6949] [PMID: 26799422]
[26]
Lu, H.; Ju, D.D.; Yang, G.D.; Zhu, L.Y.; Yang, X.M.; Li, J.; Song, W.W.; Wang, J.H.; Zhang, C.C.; Zhang, Z.G.; Zhang, R. Targeting cancer stem cell signature gene SMOC-2 Overcomes chemoresistance and inhibits cell proliferation of endometrial carcinoma. EBioMedicine, 2019, 40, 276-289.
[http://dx.doi.org/10.1016/j.ebiom.2018.12.044] [PMID: 30594556]
[27]
Zhang, H.H.; Huang, B.; Cao, Y.H.; Li, Q.; Xu, H.F. Role of 5-Aza-CdR in mitomycin-C chemosensitivity of T24 bladder cancer cells. Oncol. Lett., 2017, 14(5), 5652-5656.
[http://dx.doi.org/10.3892/ol.2017.6853] [PMID: 29142609]
[28]
Godoy, G.; Gakis, G.; Smith, C.L.; Fahmy, O. Effects of androgen and estrogen receptor signaling pathways on bladder cancer initiation and progression. Bladder Cancer, 2016, 2(2), 127-137.
[http://dx.doi.org/10.3233/BLC-160052] [PMID: 27376135]
[29]
Chaffer, C.L.; Brennan, J.P.; Slavin, J.L.; Blick, T.; Thompson, E.W.; Williams, E.D. Mesenchymal-to-epithelial transition facilitates bladder cancer metastasis: Role of fibroblast growth factor receptor-2. Cancer Res., 2006, 66(23), 11271-11278.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-2044] [PMID: 17145872]
[30]
Gugnoni, M.; Sancisi, V.; Gandolfi, G.; Manzotti, G.; Ragazzi, M.; Giordano, D.; Tamagnini, I.; Tigano, M.; Frasoldati, A.; Piana, S.; Ciarrocchi, A. Cadherin-6 promotes EMT and cancer metastasis by restraining autophagy. Oncogene, 2017, 36(5), 667-677.
[http://dx.doi.org/10.1038/onc.2016.237] [PMID: 27375021]
[31]
Li, S.; Cong, X.; Gao, H.; Lan, X.; Li, Z.; Wang, W.; Song, S.; Wang, Y.; Li, C.; Zhang, H.; Zhao, Y.; Xue, Y. Tumor-associated neutrophils induce EMT by IL-17a to promote migration and invasion in gastric cancer cells. J. Exp. Clin. Cancer Res., 2019, 38(1), 6.
[http://dx.doi.org/10.1186/s13046-018-1003-0] [PMID: 30616627]
[32]
Risolino, M.; Mandia, N.; Iavarone, F.; Dardaei, L.; Longobardi, E.; Fernandez, S.; Talotta, F.; Bianchi, F.; Pisati, F.; Spaggiari, L.; Harter, P.N.; Mittelbronn, M.; Schulte, D.; Incoronato, M.; Di Fiore, P.P.; Blasi, F.; Verde, P. Transcription factor PREP1 induces EMT and metastasis by controlling the TGF-β-SMAD3 pathway in non-small cell lung adenocarcinoma. Proc. Natl. Acad. Sci. USA, 2014, 111(36), E3775-E3784.
[http://dx.doi.org/10.1073/pnas.1407074111] [PMID: 25157139]
[33]
Zhu, X.; Wei, L.; Bai, Y.; Wu, S.; Han, S. FoxC1 promotes epithelial-mesenchymal transition through PBX1 dependent transactivation of ZEB2 in esophageal cancer. Am. J. Cancer Res., 2017, 7(8), 1642-1653.
[PMID: 28861321]
[34]
Zhuang, C.; Ma, Q.; Zhuang, C.; Ye, J.; Zhang, F.; Gui, Y. LncRNA GClnc1 promotes proliferation and invasion of bladder cancer through activation of MYC. FASEB J., 2019, 33(10), 11045-11059.
[http://dx.doi.org/10.1096/fj.201900078RR] [PMID: 31298933]
[35]
Long, Y.; Wu, Z.; Yang, X.; Chen, L.; Han, Z.; Zhang, Y.; Liu, J.; Liu, W.; Liu, X. MicroRNA-101 inhibits the proliferation and invasion of bladder cancer cells via targeting c-FOS. Mol. Med. Rep., 2016, 14(3), 2651-2656.
[http://dx.doi.org/10.3892/mmr.2016.5534] [PMID: 27485165]
[36]
Hsu, I.; Vitkus, S.; Da, J.; Yeh, S. Role of oestrogen receptors in bladder cancer development. Nat. Rev. Urol., 2013, 10(6), 317-326.
[http://dx.doi.org/10.1038/nrurol.2013.53] [PMID: 23588401]
[37]
Wolpert, B.J.; Amr, S.; Ezzat, S.; Saleh, D.; Gouda, I.; Loay, I.; Hifnawy, T.; Mikhail, N.N.; Abdel-Hamid, M.; Zhan, M.; Zheng, Y.L.; Squibb, K.; Abdel-Aziz, M.A.; Zaghloul, M.; Khaled, H.; Loffredo, C.A. Estrogen exposure and bladder cancer risk in Egyptian women. Maturitas, 2010, 67(4), 353-357.
[http://dx.doi.org/10.1016/j.maturitas.2010.07.014] [PMID: 20813471]
[38]
Miyamoto, H.; Yang, Z.; Chen, Y.T.; Ishiguro, H.; Uemura, H.; Kubota, Y.; Nagashima, Y.; Chang, Y.J.; Hu, Y.C.; Tsai, M.Y.; Yeh, S.; Messing, E.M.; Chang, C. Promotion of bladder cancer development and progression by androgen receptor signals. J. Natl. Cancer Inst., 2007, 99(7), 558-568.
[http://dx.doi.org/10.1093/jnci/djk113] [PMID: 17406000]
[39]
Izumi, K.; Zheng, Y.; Hsu, J.W.; Chang, C.; Miyamoto, H. Androgen receptor signals regulate UDP-glucuronosyltransferases in the urinary bladder: A potential mechanism of androgen-induced bladder carcinogenesis. Mol. Carcinog., 2013, 52(2), 94-102.
[http://dx.doi.org/10.1002/mc.21833] [PMID: 22086872]
[40]
Ding, M.; Liu, Y.; Li, J.; Yao, L.; Liao, X.; Xie, H.; Yang, K.; Zhou, Q.; Liu, Y.; Huang, W.; Cai, Z. Oestrogen promotes tumorigenesis of bladder cancer by inducing the enhancer RNA-eGREB1. J. Cell. Mol. Med., 2018, 22(12), 5919-5927.
[http://dx.doi.org/10.1111/jcmm.13861] [PMID: 30252203]
[41]
Sonpavde, G.; Okuno, N.; Weiss, H.; Yu, J.; Shen, S.S.; Younes, M.; Jian, W.; Lerner, S.P.; Smith, C.L. Efficacy of selective estrogen receptor modulators in nude mice bearing human transitional cell carcinoma. Urology, 2007, 69(6), 1221-1226.
[http://dx.doi.org/10.1016/j.urology.2007.02.041] [PMID: 17572228]
[42]
Shen, S.S.; Smith, C.L.; Hsieh, J.T.; Yu, J.; Kim, I.Y.; Jian, W.; Sonpavde, G.; Ayala, G.E.; Younes, M.; Lerner, S.P. Expression of estrogen receptors-alpha and -beta in bladder cancer cell lines and human bladder tumor tissue. Cancer, 2006, 106(12), 2610-2616.
[http://dx.doi.org/10.1002/cncr.21945] [PMID: 16700038]
[43]
Su, Y.; Yang, W.; Jiang, N.; Shi, J.; Chen, L.; Zhong, G.; Bi, J.; Dong, W.; Wang, Q.; Wang, C.; Lin, T. Hypoxia-elevated circELP3 contributes to bladder cancer progression and cisplatin resistance. Int. J. Biol. Sci., 2019, 15(2), 441-452.
[http://dx.doi.org/10.7150/ijbs.26826] [PMID: 30745833]
[44]
Zhang, Y.; Wang, Z.; Yu, J.; Shi, J.; Wang, C.; Fu, W.; Chen, Z.; Yang, J. Cancer stem-like cells contribute to cisplatin resistance and progression in bladder cancer. Cancer Lett., 2012, 322(1), 70-77.
[http://dx.doi.org/10.1016/j.canlet.2012.02.010] [PMID: 22343321]
[45]
Ghosh, S. Cisplatin: The first metal based anticancer drug. Bioorg. Chem., 2019, 88, 102925.
[http://dx.doi.org/10.1016/j.bioorg.2019.102925] [PMID: 31003078]
[46]
Sekino, Y.; Sakamoto, N.; Ishikawa, A.; Honma, R.; Shigematsu, Y.; Hayashi, T.; Sentani, K.; Oue, N.; Teishima, J.; Matsubara, A.; Yasui, W. Transcribed ultraconserved region Uc.63+ promotes resistance to cisplatin through regulation of androgen receptor signaling in bladder cancer. Oncol. Rep., 2019, 41(5), 3111-3118.
[http://dx.doi.org/10.3892/or.2019.7039] [PMID: 30864720]
[47]
Fang, C.H.; Lin, Y.T.; Liang, C.M.; Liang, S.M. A novel c-Kit/phospho-prohibitin axis enhances ovarian cancer stemness and chemoresistance via Notch3-PBX1 and β-catenin-ABCG2 signaling. J. Biomed. Sci., 2020, 27(1), 42.
[http://dx.doi.org/10.1186/s12929-020-00638-x] [PMID: 32169072]

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