SOX2 promotes lineage plasticity and antiandrogen resistance in TP53-and RB1-deficient prostate cancer

被引：793

作者：

Mu, Ping ^{[1
]}

Zhang, Zeda ^{[1
]}

Benelli, Matteo

Karthaus, Wouter R.

Hoover, Elizabeth ^{[7
,10
]}

Chen, Chi-Chao ^{[6
]}

Wongvipat, John ^{[5
,8
]}

Ku, Sheng-Yu ^{[10
]}

Gao, Dong ^{[3
]}

Cao, Zhen ^{[7
]}

Shah, Neel ^{[4
]}

Adams, Elizabeth J.

Abida, Wassim

Watson, Philip A. ^{[5
]}

Prandi, Davide ^{[3
]}

Huang, Chun-Hao

de Stanchina, Elisa ^{[2
,3
,4
,7
]}

Lowe, Scott W. ^{[5
,6
]}

Ellis, Leigh ^{[2
,5
]}

Beltran, Himisha ^{[4
,10
]}

Rubin, Mark A.

Goodrich, David W.

Demichelis, Francesca

Sawyers, Charles L. ^{[1
,9
]}

机构：

[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

来源：

SCIENCE | 2017年 / 355卷 / 6320期

基金：

欧洲研究理事会;

关键词：

STEM-CELL; LUNG; GENE; PLURIPOTENCY; SUPPRESSION; CARCINOMAS; INHIBITORS; EVOLUTION; MUTATION; BARRIER;

D O I：

10.1126/science.aah4307

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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.

引用

页码：84 / 88

页数：5

共 31 条

[1]

[Anonymous], 2015, CELL, V163, P1011, DOI [10.1016/j.cell.2015.10.025, DOI 10.1016/J.CELL.2015.10.025]

[2] Combined Tumor Suppressor Defects Characterize Clinically Defined Aggressive Variant Prostate Cancers [J].

Aparicio, Ana M. ;

Shen, Li ;

Tapia, Elsa Li Ning ;

Lu, Jing-Fang ;

Chen, Hsiang-Chun ;

Zhang, Jiexin ;

Wu, Guanglin ;

Wang, Xuemei ;

Troncoso, Patricia ;

Corn, Paul ;

Thompson, Timothy C. ;

Broom, Bradley ;

Baggerly, Keith ;

Maity, Sankar N. ;

Logothetis, Christopher J. .

CLINICAL CANCER RESEARCH, 2016, 22 (06) :1520-1530

[3] Glucocorticoid Receptor Confers Resistance to Antiandrogens by Bypassing Androgen Receptor Blockade [J].

Arora, Vivek K. ;

Schenkein, Emily ;

Murali, Rajmohan ;

Subudhi, Sumit K. ;

Wongvipat, John ;

Balbas, Minna D. ;

Shah, Neel ;

Cai, Ling ;

Efstathiou, Eleni ;

Logothetis, Chris ;

Zheng, Deyou ;

Sawyers, Charles L. .

CELL, 2013, 155 (06) :1309-1322

[4] Overcoming mutation-based resistance to antiandrogens with rational drug design [J].

Balbas, Minna D. ;

Evans, Michael J. ;

Hosfield, David J. ;

Wongvipat, John ;

Arora, Vivek K. ;

Watson, Philip A. ;

Chen, Yu ;

Greene, Geoffrey L. ;

Shen, Yang ;

Sawyers, Charles L. .

ELIFE, 2013, 2

[5] SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas [J].

Bass, Adam J. ;

Watanabe, Hideo ;

Mermel, Craig H. ;

Yu, Soyoung ;

Perner, Sven ;

Verhaak, Roel G. ;

Kim, So Young ;

Wardwell, Leslie ;

Tamayo, Pablo ;

Gat-Viks, Irit ;

Ramos, Alex H. ;

Woo, Michele S. ;

Weir, Barbara A. ;

Getz, Gad ;

Beroukhim, Rameen ;

O'Kelly, Michael ;

Dutt, Amit ;

Rozenblatt-Rosen, Orit ;

Dziunycz, Piotr ;

Komisarof, Justin ;

Chirieac, Lucian R. ;

LaFargue, Christopher J. ;

Scheble, Veit ;

Wilbertz, Theresia ;

Ma, Changqing ;

Rao, Shilpa ;

Nakagawa, Hiroshi ;

Stairs, Douglas B. ;

Lin, Lin ;

Giordano, Thomas J. ;

Wagner, Patrick ;

Minna, John D. ;

Gazdar, Adi F. ;

Zhu, Chang Qi ;

Brose, Marcia S. ;

Cecconello, Ivan ;

Ribeiro, Ulysses, Jr. ;

Marie, Suely K. ;

Dahl, Olav ;

Shivdasani, Ramesh A. ;

Tsao, Ming-Sound ;

Rubin, Mark A. ;

Wong, Kwok K. ;

Regev, Aviv ;

Hahn, William C. ;

Beer, David G. ;

Rustgi, Anil K. ;

Meyerson, Matthew .

NATURE GENETICS, 2009, 41 (11) :1238-U105

[6] Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer [J].

Beltran, Himisha ;

Prandi, Davide ;

Mosquera, Juan Miguel ;

Benelli, Matteo ;

Puca, Loredana ;

Cyrta, Joanna ;

Marotz, Clarisse ;

Giannopoulou, Eugenia ;

Chakravarthi, Balabhadrapatruni V. S. K. ;

Varambally, Sooryanarayana ;

Tomlins, Scott A. ;

Nanus, David M. ;

Tagawa, Scott T. ;

Van Allen, Eliezer M. ;

Elemento, Olivier ;

Sboner, Andrea ;

Garraway, Levi A. ;

Rubin, Mark A. ;

Demichelis, Francesca .

NATURE MEDICINE, 2016, 22 (03) :298-305

[7] Molecular Characterization of Neuroendocrine Prostate Cancer and Identification of New Drug Targets [J].

Beltran, Himisha ;

Rickman, David S. ;

Park, Kyung ;

Chae, Sung Suk ;

Sboner, Andrea ;

MacDonald, Theresa Y. ;

Wang, Yuwei ;

Sheikh, Karen L. ;

Terry, Stephane ;

Tagawa, Scott T. ;

Dhir, Rajiv ;

Nelson, Joel B. ;

de la Taille, Alexandre ;

Allory, Yves ;

Gerstein, Mark B. ;

Perner, Sven ;

Pienta, Kenneth J. ;

Chinnaiyan, Arul M. ;

Wang, Yuzhuo ;

Collins, Colin C. ;

Gleave, Martin E. ;

Demichelis, Francesca ;

Nanus, David M. ;

Rubin, Mark A. .

CANCER DISCOVERY, 2011, 1 (06) :487-495

[8] Rb regulates fate choice and lineage commitment in vivo [J].

Calo, Eliezer ;

Quintero-Estades, Jose A. ;

Danielian, Paul S. ;

Nedelcu, Simona ;

Berman, Seth D. ;

Lees, Jacqueline A. .

NATURE, 2010, 466 (7310) :1110-U126

[9] miR-34 miRNAs provide a barrier for somatic cell reprogramming [J].

Choi, Yong Jin ;

Lin, Chao-Po ;

Ho, Jaclyn J. ;

He, Xingyue ;

Okada, Nobuhiro ;

Bu, Pengcheng ;

Zhong, Yingchao ;

Kim, Sang Yong ;

Bennett, Margaux J. ;

Chen, Caifu ;

Ozturk, Arzu ;

Hicks, Geoffrey G. ;

Hannon, Greg J. ;

He, Lin .

NATURE CELL BIOLOGY, 2011, 13 (11) :1353-U154

[10] The Comparative Pathology of Genetically Engineered Mouse Models for Neuroendocrine Carcinomas of the Lung [J].

Gazdar, Adi F. ;

Savage, Trisha K. ;

Johnson, Jane E. ;

Berns, Anton ;

Sage, Julien ;

Linnoila, R. Ilona ;

MacPherson, David ;

McFadden, David G. ;

Farago, Anna ;

Jacks, Tyler ;

Travis, William D. ;

Brambilla, Elisabeth .

JOURNAL OF THORACIC ONCOLOGY, 2015, 10 (04) :553-564

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