title: TR4 Nuclear Receptor Alters the Prostate Cancer CD133+ Stem/Progenitor Cell Invasion via Modulating the EZH2-Related Metastasis Gene Expression.
abstract: 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, TGFβ1, 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.
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China. 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.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China. 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.
authors.forename: Dong-Rong
authors.initials: DR
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Yin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 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. Department of Urology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China.
authors.forename: Xiaofu
authors.initials: X
authors.lastname: Qiu
authors.affiliation: 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. Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hong-Chiang
authors.initials: HC
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Gonghui
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China. 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. chang@urmc.rochester.edu shanyx1002@aliyun.com.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Shan
authors.affiliation: 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. Sex Hormone Research Center, China Medical University/Hospital, Taichung, Taiwan. chang@urmc.rochester.edu shanyx1002@aliyun.com.
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D000071221:Enhancer of Zeste Homolog 2 Protein; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D034622:RNA Interference; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C490515:NR2C2 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D051881:Receptor, Notch1; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D053773:Transforming Growth Factor beta1; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
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