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DOI | 10.1038/s41467-019-08855-1 |
Thioredoxin-1 protects against androgen receptor-induced redox vulnerability in castration-resistant prostate cancer | |
Samaranayake, Govindi J.1,2; Troccoli, Clara I.1,2; Huynh, Mai2,3; Lyles, Rolando D. Z.1,2; Kage, Karen2; Win, Andrew2,3; Lakshmanan, Vishalakshi2,3; Kwon, Deukwoo4; Ban, Yuguang4; Chen, Steven Xi4,5; Zarco, Enrique Rodriguez6; Jorda, Merce4,6; Burnstein, Kerry L.4,7; Rai, Priyamvada2,4 | |
2019-03-06 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Androgen deprivation (AD) therapy failure leads to terminal and incurable castration-resistant prostate cancer (CRPC). We show that the redox-protective protein thioredoxin-1 (TRX1) increases with prostate cancer progression and in androgen-deprived CRPC cells, suggesting that CRPC possesses an enhanced dependency on TRX1. TRX1 inhibition via shRNA or a phase I-approved inhibitor, PX-12 (untested in prostate cancer), impedes the growth of CRPC cells to a greater extent than their androgen-dependent counterparts. TRX1 inhibition elevates reactive oxygen species (ROS), p53 levels and cell death in androgen-deprived CRPC cells. Unexpectedly, TRX1 inhibition also elevates androgen receptor (AR) levels under AD, and AR depletion mitigates both TRX1 inhibition-mediated ROS production and cell death, suggesting that AD-resistant AR expression in CRPC induces redox vulnerability. In vivo TRX1 inhibition via shRNA or PX-12 reverses the castration-resistant phenotype of CRPC cells, significantly inhibiting tumor formation under systemic AD. Thus, TRX1 is an actionable CRPC therapeutic target through its protection against AR-induced redox stress. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000414032200007 |
WOS关键词 | OXIDATIVE STRESS ; INCREASED EXPRESSION ; GENE-EXPRESSION ; PREMATURE SENESCENCE ; ANTIOXIDANT DEFENSE ; ANTITUMOR-ACTIVITY ; HYDROGEN-PEROXIDE ; DNA-REPAIR ; INHIBITOR ; GROWTH |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204247 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Miami, Miller Sch Med, Sheila & David Fuente Grad Program Canc Biol, Miami, FL 33136 USA; 2.Univ Miami, Miller Sch Med, Dept Med, Med Oncol, Miami, FL 33136 USA; 3.Univ Miami, Undergrad Res & Community Outreach Program, Ungar Bldg,Mem Dr, Coral Gables, FL 33146 USA; 4.Sylvester Comprehens Canc Ctr, 1475NW 12th Ave, Miami, FL 33136 USA; 5.Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, Miami, FL 33136 USA; 6.Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA; 7.Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA |
推荐引用方式 GB/T 7714 | Samaranayake, Govindi J.,Troccoli, Clara I.,Huynh, Mai,et al. Thioredoxin-1 protects against androgen receptor-induced redox vulnerability in castration-resistant prostate cancer[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Samaranayake, Govindi J..,Troccoli, Clara I..,Huynh, Mai.,Lyles, Rolando D. Z..,Kage, Karen.,...&Rai, Priyamvada.(2019).Thioredoxin-1 protects against androgen receptor-induced redox vulnerability in castration-resistant prostate cancer.NATURE COMMUNICATIONS,8. |
MLA | Samaranayake, Govindi J.,et al."Thioredoxin-1 protects against androgen receptor-induced redox vulnerability in castration-resistant prostate cancer".NATURE COMMUNICATIONS 8(2019). |
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