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DOI | 10.1126/science.aah4307 |
SOX2 promotes lineage plasticity and antiandrogen resistance in TP53-and RB1-deficient prostate cancer | |
Mu, Ping1; Zhang, Zeda1; Benelli, Matteo; Karthaus, Wouter R.; Hoover, Elizabeth7,10; Chen, Chi-Chao6; Wongvipat, John5,8; Ku, Sheng-Yu10; Gao, Dong3; Cao, Zhen7; Shah, Neel4; Adams, Elizabeth J.; Abida, Wassim; Watson, Philip A.5; Prandi, Davide3; Huang, Chun-Hao; de Stanchina, Elisa2,3,4,7; Lowe, Scott W.5,6; Ellis, Leigh2,5; Beltran, Himisha4,10; Rubin, Mark A.; Goodrich, David W.; Demichelis, Francesca; Sawyers, Charles L.1,9 | |
2017-01-06 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 355期号:6320页码:84-88 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Italy |
英文摘要 | Some cancers evade targeted therapies through a mechanism known as lineage plasticity, whereby tumor cells acquire phenotypic characteristics of a cell lineage whose survival no longer depends on the drug target. We use in vitro and in vivo human prostate cancer models to show that these tumors can develop resistance to the antiandrogen drug enzalutamide by a phenotypic shift from androgen receptor (AR)-dependent luminal epithelial cells to AR-independent basal-like cells. This lineage plasticity is enabled by the loss of TP53 and RB1 function, is mediated by increased expression of the reprogramming transcription factor SOX2, and can be reversed by restoring TP53 and RB1 function or by inhibiting SOX2 expression. Thus, mutations in tumor suppressor genes can create a state of increased cellular plasticity that, when challenged with antiandrogen therapy, promotes resistance through lineage switching. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000391739900048 |
WOS关键词 | STEM-CELL ; LUNG ; GENE ; PLURIPOTENCY ; SUPPRESSION ; CARCINOMAS ; INHIBITORS ; EVOLUTION ; MUTATION ; BARRIER |
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/195161 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Mem Sloan Kettering Canc Ctr, Human Oncol & Pathol Program, 1275 York Ave, New York, NY 10065 USA; 2.Mem Sloan Kettering Canc Ctr, Louis V Gerstner Jr Grad Sch Biomed Sci, New York, NY 10065 USA; 3.Univ Trento, Ctr Integrat Biol, Trento, Italy; 4.Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10065 USA; 5.Cornell Univ, Weill Cornell Grad Sch Med Sci, New York, NY 10021 USA; 6.Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, New York, NY 14263 USA; 7.Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol, 1275 York Ave, New York, NY 10065 USA; 8.Howard Hughes Med Inst, Chevy Chase, MD 20815 USA; 9.Weill Cornell Med & New York Presbyterian Hosp, Englander Inst Precis Med, New York, NY 10065 USA; 10.Sandra & Edward Meyer Canc Ctr, Weill Cornell Med, York, NY 10021 USA |
推荐引用方式 GB/T 7714 | Mu, Ping,Zhang, Zeda,Benelli, Matteo,et al. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53-and RB1-deficient prostate cancer[J]. SCIENCE,2017,355(6320):84-88. |
APA | Mu, Ping.,Zhang, Zeda.,Benelli, Matteo.,Karthaus, Wouter R..,Hoover, Elizabeth.,...&Sawyers, Charles L..(2017).SOX2 promotes lineage plasticity and antiandrogen resistance in TP53-and RB1-deficient prostate cancer.SCIENCE,355(6320),84-88. |
MLA | Mu, Ping,et al."SOX2 promotes lineage plasticity and antiandrogen resistance in TP53-and RB1-deficient prostate cancer".SCIENCE 355.6320(2017):84-88. |
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