TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer.
TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer.
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DOI：
10.1016/j.ccell.2016.04.012
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发表时间：
2016-06-13
期刊：
影响因子：
50.3
通讯作者：
Brown M
中科院分区：
文献类型：
--
作者：
Groner AC;Cato L;de Tribolet-Hardy J;Bernasocchi T;Janouskova H;Melchers D;Houtman R;Cato ACB;Tschopp P;Gu L;Corsinotti A;Zhong Q;Fankhauser C;Fritz C;Poyet C;Wagner U;Guo T;Aebersold R;Garraway LA;Wild PJ;Theurillat JP;Brown M
雄激素受体(AR)信号转导是前列腺癌(PC)的关键驱动因素。虽然去雄激素治疗对晚期疾病是短暂有效的，但肿瘤通常进展到致命的去势抵抗状态(CRPC)。我们表明，SPOP中反复出现的PC驱动突变稳定了TRIM24蛋白，后者在低雄激素条件下促进了增殖。TRIM24增强AR信号，AR和TRIM24共激活基因在CRPC中显著上调。从原发PC到CRPC，TRIM24蛋白表达增加，TRIM24蛋白水平和AR/TRIM24基因标志均预示疾病复发。在CRPC细胞中的分析表明，TRIM24溴结构域和AR相互作用基序是支持增殖所必需的。这些数据为SPOP突变和CRPC患者的TRIM24靶向治疗提供了理论依据。
Androgen receptor (AR) signaling is a key driver of prostate cancer (PC). While androgen-deprivation therapy is transiently effective in advanced disease, tumors often progress to a lethal castration-resistant state (CRPC). We show that recurrent PC-driver mutations in SPOP stabilize the TRIM24 protein, which promotes proliferation under low androgen conditions. TRIM24 augments AR signaling, and AR and TRIM24 co-activated genes are significantly up-regulated in CRPC. Expression of TRIM24 protein increases from primary PC to CRPC, and both TRIM24 protein levels and the AR/TRIM24 gene signature predict disease-recurrence. Analyses in CRPC cells reveal that the TRIM24 bromodomain and the AR-interacting motif are essential to support proliferation. These data provide a rationale for therapeutic TRIM24 targeting in SPOP-mutant and CRPC patients.
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影响因子：
7.3
作者：
Bennett J;Fedorov O;Tallant C;Monteiro O;Meier J;Gamble V;Savitsky P;Nunez-Alonso GA;Haendler B;Rogers C;Brennan PE;Müller S;Knapp S
通讯作者：
Knapp S
影响因子：
4.5
作者：
Hazelett DJ;Rhie SK;Gaddis M;Yan C;Lakeland DL;Coetzee SG;Ellipse/GAME-ON consortium;Practical consortium;Henderson BE;Noushmehr H;Cozen W;Kote-Jarai Z;Eeles RA;Easton DF;Haiman CA;Lu W;Farnham PJ;Coetzee GA
通讯作者：
Coetzee GA
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
4.8
作者：
Blattner, Mirjam;Lee, Daniel J.;Rubin, Mark A.
通讯作者：
Rubin, Mark A.
影响因子：
64.5
作者：
Baca SC;Prandi D;Lawrence MS;Mosquera JM;Romanel A;Drier Y;Park K;Kitabayashi N;MacDonald TY;Ghandi M;Van Allen E;Kryukov GV;Sboner A;Theurillat JP;Soong TD;Nickerson E;Auclair D;Tewari A;Beltran H;Onofrio RC;Boysen G;Guiducci C;Barbieri CE;Cibulskis K;Sivachenko A;Carter SL;Saksena G;Voet D;Ramos AH;Winckler W;Cipicchio M;Ardlie K;Kantoff PW;Berger MF;Gabriel SB;Golub TR;Meyerson M;Lander ES;Elemento O;Getz G;Demichelis F;Rubin MA;Garraway LA
通讯作者：
Garraway LA