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| 題名: | Methylosome protein 50 promotes androgen- and estrogen-independent tumorigenesis |
| 作者: | 蘇立仁;Wei, Tong-You Wade;Hsia, Jiun-Yi;Chiu, Shao-Chih;Su, Li-Jen;Juan, Chi-Chang;Lee, Yuan-Chii Gladys;Chen, Jo-Mei Maureen;Chou, Hsiang-Yun;Huang, Jiao-Ying;Huang, Hiang-Ming;Yu, Chang-Tze Ricky |
| 貢獻者: | 生醫理工學院生醫科學與工程學系 |
| 關鍵詞: | Activated;Adaptor Proteins, Signal Transducing - genetics;Adaptor Proteins, Signal Transducing - metabolism;AKT;Androgen;Androgens - metabolism;Animals;Cancer;Carcinogenesis - metabolism;Cell Line, Tumor;Cell Movement - genetics;Cell Proliferation;Cell Transformation, Neoplastic - genetics;Cell Transformation, Neoplastic - pathology;Estrogen;Estrogen Receptor alpha - metabolism;Estrogens;Estrogens - metabolism;G2 Phase;Gene Expression Regulation, Neoplastic;Humans;Inhibitors;Kinases;Lung Neoplasms - genetics;Lung Neoplasms - pathology;MEP50;Methylation;Mice, Inbred BALB C;Mice, Nude;Migration;Neoplasm Proteins - metabolism;Phosphatidylinositol 3-Kinases - metabolism;PI3K;PRMT5;Protein-Arginine N-Methyltransferases - metabolism;Proteins;Proto-Oncogene Proteins c-akt - metabolism;Receptors, Androgen - metabolism;Signal Transduction;Transforms;Up-Regulation |
| 日期: | 2014-09-01 |
| 上傳時間: | 2026-04-23 11:17:06 (UTC+8) |
| 出版者: | Elsevier Inc.;England: Elsevier Inc |
| 摘要: | 摘要： Methylosome protein 50 (MEP50) is a component of methylosome where MEP50 binds protein substrates and activates the oncogenic protein arginine methyl transferase 5 (PRMT5). MEP50 is also a coactivator for androgen receptor (AR) and estrogen receptor (ER), and transforms cells in the presence of androgen or estrogen. To extend the understanding of how MEP50 transforms cells, we investigated whether MEP50 could transform cells independent of AR and ER, and clarified whether PRMT5 could contribute to the MEP50-caused tumor formation. Microarray and Western blot analyses revealed the association of MEP50 with many human cancers including lung cancer. Knockdown of MEP50 retarded cell growth and migration in selected lung cancer cell lines, which expressed very low level of AR and ER and were insensitive to inhibitors of AR and ER. Moreover, overexpression of Myc-MEP50 enhanced cell transforming activities of 293T cells which are known lack of expression of AR and ER. Mechanistic analyses showed that MEP50 controlled G2 progression, upregulated cyclin-dependent kinase 1(CDK1)/cyclin B1, and activated the survival cascade Phosphoinositide 3-kinase (PI3K)/AKT. MEP50 promoted cell migration, and activated the cell migration pathways such as Ras-related C3 botulinum toxin substrate 1 (Rac1)/vasodilator-stimulated phosphoprotein (VASP), and forkhead box protein A2 (FOXA2)/slug/cadherin cascades. Further analyses revealed that MEP50 activated the survival factor PI3K through PRMT5-catalyzed dimethylation of PI3K. Collectively, it is concluded that MEP50 can transform cells independent of AR and ER, and PRMT5 has partial contribution to that process. •MEP50 promotes cell transforming activities of lung cancer cell lines with limited ER or AR activity.•MEP50 transforms 293T cells which do not express ER and AR.•MEP50 stimulates G2 progression and upregulates CDK1 and cyclin B in 293T.•MEP50 enhances cell migration by adopting Rac1/VASP and FOXA2/Slug/Cadherins cascades in 293T.•MEP50 promotes cell survival by employing PRMT5/PI3K in 293T.
其他題名： Cell Signal
出版者： England: Elsevier Inc
出版日期： 2014-12-01
出處： Cellular signalling, 2014-12, Vol.26 (12), p.2940-2950
版權： 2014 Elsevier Inc.
版權： Copyright © 2014 Elsevier Inc. All rights reserved.
識別號： ISSN: 0898-6568
識別號： ISSN: 1873-3913
識別號： EISSN: 1873-3913
識別號： DOI: 10.1016/j.cellsig.2014.09.014
識別號： PMID: 25277535 |
| 顯示於類別: | [生醫科學與工程學系] 期刊論文
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