https://scholars.lib.ntu.edu.tw/handle/123456789/541948
標題: | TR4 nuclear receptor alters the prostate cancer CD133+ stem/progenitor cell invasion via modulating the EZH2-related metastasis gene expression | 作者: | Zhu J. Yang D.-R. Sun Y. Qiu X. HONG-CHIANG CHANG Li G. Shan Y. Chang C. |
公開日期: | 2015 | 出版社: | American Association for Cancer Research Inc. | 卷: | 14 | 期: | 6 | 起(迄)頁: | 1445-1453 | 來源出版物: | Molecular Cancer Therapeutics | 摘要: | 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 50 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. ? 2015 American Association for Cancer Research. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84930957605&doi=10.1158%2f1535-7163.MCT-14-0971&partnerID=40&md5=c9c4ca6311914c552c762fc70153f0d5 https://scholars.lib.ntu.edu.tw/handle/123456789/541948 |
ISSN: | 1535-7163 | DOI: | 10.1158/1535-7163.MCT-14-0971 | SDG/關鍵字: | CD133 antigen; cell nucleus receptor; gelatinase B; Notch1 receptor; testicular nuclear receptor 4; transcription factor EZH2; transcription factor Slug; transforming growth factor beta1; unclassified drug; CD133 antigen; EZH2 protein, human; glycoprotein; leukocyte antigen; Notch1 receptor; NR2C2 protein, human; peptide; polycomb repressive complex 2; PROM1 protein, human; Prom1 protein, mouse; protein binding; steroid receptor; thyroid hormone receptor; transcription factor EZH2; transforming growth factor beta1; animal experiment; animal model; animal tissue; Article; cancer stem cell; cancer therapy; cell invasion; controlled study; gene expression regulation; gene repression; gene silencing; gene targeting; in vitro study; in vivo study; male; metastasis; mouse; nonhuman; oncogene; priority journal; promoter region; prostate cancer; protein binding; protein function; signal transduction; transcription regulation; animal; cancer stem cell; cell culture; cell motion; genetics; human; metabolism; metastasis; nude mouse; pathology; prostate tumor; reverse transcription polymerase chain reaction; RNA interference; tumor cell line; Western blotting; xenograft; AC133 Antigen; Animals; Antigens, CD; Blotting, Western; Cell Line, Tumor; Cell Movement; Cells, Cultured; Enhancer of Zeste Homolog 2 Protein; Gene Expression Regulation, Neoplastic; Glycoproteins; Humans; Male; Mice, Nude; Neoplasm Metastasis; Neoplastic Stem Cells; Peptides; Polycomb Repressive Complex 2; Promoter Regions, Genetic; Prostatic Neoplasms; Protein Binding; Receptor, Notch1; Receptors, Steroid; Receptors, Thyroid Hormone; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Transforming Growth Factor beta1; Transplantation, Heterologous |
顯示於: | 醫學系 |
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