机构：[1]Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China.[2]George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York.[3]Department of Urology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China.[4]Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.[5]Sex Hormone Research Center, China Medical University/Hospital, Taichung, Taiwan.
The testicular nuclear receptor 4 (TR4) is a member of the nuclear receptor superfamily that mediates various biologic functions with key impacts on metabolic disorders and tumor progression. Here, we demonstrate that TR4 may play a positive role in prostate cancer CD133(+) stem/progenitor (S/P) cell invasion. Targeting TR4 with lentiviral silencing RNA significantly suppressed prostate cancer CD133(+) S/P cell invasion both in vitro and in vivo. Mechanism dissection found that TR4 transcriptionally regulates the oncogene EZH2 via binding to its 5' promoter region. The consequences of targeting TR4 to suppress EZH2 expression may then suppress the expression of its downstream key metastasis-related genes, including NOTCH1, TGF beta 1, SLUG, and MMP9. Rescue approaches via adding the EZH2 reversed the TR4-mediated prostate cancer S/P cell invasion. Together, these results suggest that the TR4, EZH2 signaling may play a critical role in the prostate cancer S/P cell invasion and may allow us to develop a better therapy to battle the prostate cancer metastasis. (C) 2015 AACR.
基金：
This work was supported by NIH grants (CA122840 and CA156700; to C
Chang), George Whipple Professorship Endowment (to C. Chang), the Taiwan
Department of Health Clinical Trial (to C. Chang), Research Center of Excellence
(DOH99-TD-B-111-004 to China Medical University, Taichung, Taiwan;
to C. Chang), and NSFC (Grant No. 81472776; to D.-R. Yang).
第一作者机构：[1]Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China.[2]George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York.
共同第一作者：
通讯作者：
通讯机构：[*1]George Whipple Lab for Cancer Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, 14642 NY.[*2]Department of Urology, the Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road Suzhou 215004,China.
推荐引用方式(GB/T 7714)：
Jin Zhu,Dong-Rong Yang,Yin Sun,et al.TR4 Nuclear Receptor Alters the Prostate Cancer CD133(+) Stem/Progenitor Cell Invasion via Modulating the EZH2-Related Metastasis Gene Expression[J].MOLECULAR CANCER THERAPEUTICS.2015,14(6):1445-53.doi:10.1158/1535-7163.MCT-14-0971.
APA：
Jin Zhu,Dong-Rong Yang,Yin Sun,Xiaofu Qiu,Hong-Chiang Chang...&Chawnshang Chang.(2015).TR4 Nuclear Receptor Alters the Prostate Cancer CD133(+) Stem/Progenitor Cell Invasion via Modulating the EZH2-Related Metastasis Gene Expression.MOLECULAR CANCER THERAPEUTICS,14,(6)
MLA：
Jin Zhu,et al."TR4 Nuclear Receptor Alters the Prostate Cancer CD133(+) Stem/Progenitor Cell Invasion via Modulating the EZH2-Related Metastasis Gene Expression".MOLECULAR CANCER THERAPEUTICS 14..6(2015):1445-53
