The Placental Gene PEG10 Promotes Progression of Neuroendocrine Prostate Cancer

被引：256

作者：

Akamatsu, Shusuke ^{[1
,2
]}

Wyatt, Alexander W. ^{[1
,2
]}

Lin, Dong ^{[1
,2
,3
]}

Lysakowski, Summer ^{[1
,2
]}

Zhang, Fan ^{[1
,2
]}

Kim, Soojin ^{[1
,2
]}

Tse, Charan ^{[1
,2
]}

Wang, Kendric ^{[1
,2
]}

Mo, Fan ^{[1
,2
]}

Haegert, Anne ^{[1
,2
]}

Brahmbhatt, Sonal ^{[1
,2
]}

Bell, Robert ^{[1
,2
]}

Adomat, Hans ^{[1
,2
]}

Kawai, Yoshihisa ^{[1
,2
]}

Xue, Hui ^{[3
]}

Dong, Xin ^{[3
]}

Fazli, Ladan ^{[1
,2
]}

Tsai, Harrison ^{[4
]}

Lotan, Tamara L. ^{[4
]}

Kossai, Myriam ^{[5
,6
]}

Mosquera, Juan Miguel ^{[5
,6
]}

Rubin, Mark A. ^{[5
,6
]}

Beltran, Himisha ^{[6
,7
]}

Zoubeidi, Amina ^{[1
,2
]}

Wang, Yuzhuo ^{[1
,2
,3
]}

Gleave, Martin E. ^{[1
,2
]}

Collins, Colin C. ^{[1
,2
]}

机构：

[1] Univ British Columbia, Vancouver Prostate Ctr, Vancouver, BC V6H 3Z6, Canada

[2] Univ British Columbia, Dept Urol Sci, Vancouver, BC V6H 3Z6, Canada

[3] BC Canc Agcy, Dept Expt Therapeut, Vancouver, BC V5Z 1L3, Canada

[4] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21287 USA

[5] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA

[6] Weill Cornell Med Coll, New York Presbyterian Hosp, Inst Precis Med, New York, NY 10065 USA

[7] Weill Cornell Med Coll, Dept Med, Div Hematol & Med Oncol, New York, NY 10065 USA

来源：

CELL REPORTS | 2015年 / 12卷 / 06期

基金：

加拿大健康研究院;

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; SMALL-CELL CARCINOMA; TGF-BETA; EXPRESSION PROFILE; INCREASED SURVIVAL; TUMOR PROGRESSION; PATHWAY; DISEASE; TARGETS; SNAIL;

D O I：

10.1016/j.celrep.2015.07.012

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

More potent targeting of the androgen receptor (AR) in advanced prostate cancer is driving an increased incidence of neuroendocrine prostate cancer (NEPC), an aggressive and treatment-resistant AR-negative variant. Its molecular pathogenesis remains poorly understood but appears to require TP53 and RB1 aberration. We modeled the development of NEPC from conventional prostatic adenocarcinoma using a patient-derived xenograft and found that the placental gene PEG10 is de-repressed during the adaptive response to AR interference and subsequently highly upregulated in clinical NEPC. We found that the AR and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at distinct stages of NEPC development. In vitro, PEG10 promoted cell-cycle progression from G0/G1 in the context of TP53 loss and regulated Snail expression via TGF-beta signaling to promote invasion. Taken together, these findings show the mechanistic relevance of RB1 and TP53 loss in NEPC and suggest PEG10 as a NEPC-specific target.

引用

页码：922 / 936

页数：15

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