PRMT1 Is a Novel Regulator of Epithelial-Mesenchymal-Transition in Non-small Cell Lung Cancer

被引:97
作者
Avasarala, Sreedevi [1 ]
Van Scoyk, Michelle [1 ]
Rathinam, Manoj Kumar Karuppusamy [1 ]
Zerayesus, Sereke [1 ]
Zhao, Xiangmin [1 ]
Zhang, Wei [2 ]
Pergande, Melissa R. [3 ,4 ]
Borgia, Jeffrey A. [3 ,4 ]
DeGregori, James [5 ]
Port, J. David [6 ]
Winn, Robert A. [1 ]
Bikkavilli, Rama Kamesh [1 ]
机构
[1] Univ Illinois, Div Pulm Crit Care Sleep & Allergy, Chicago, IL 60612 USA
[2] Univ Illinois, Dept Pediat, Chicago, IL 60612 USA
[3] Rush Univ, Med Ctr, Dept Pathol, Chicago, IL 60612 USA
[4] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA
[5] Univ Colorado, Dept Biochem & Mol Genet, Aurora, CO 80045 USA
[6] Univ Colorado, Dept Med Cardiol & Pharmacol, Aurora, CO 80045 USA
基金
美国国家卫生研究院;
关键词
PROTEIN ARGININE METHYLTRANSFERASES; E-CADHERIN; UP-REGULATION; TWIST; METHYLATION; EXPRESSION; PHOSPHORYLATION; BREAST; TRANSCRIPTION; SURVIVAL;
D O I
10.1074/jbc.M114.636050
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein arginine methyl transferase 1 (PRMT1) was shown to be up-regulated in cancers and important for cancer cell proliferation. However, the role of PRMT1 in lung cancer progression and metastasis remains incompletely understood. In the present study, we show that PRMT1 is an important regulator of epithelial-mesenchymal transition (EMT), cancer cell migration, and invasion, which are essential processes during cancer progression, and metastasis. Additionally, we have identified Twist1, a basic helix-loop-helix transcription factor and a well-known E-cadherin repressor, as a novel PRMT1 substrate. Taken together, we show that PRMT1 is a novel regulator of EMT and arginine 34 (Arg-34) methylation of Twist1 as a unique "methyl arginine mark" for active E-cadherin repression. Therefore, targeting PRMT1-mediated Twist1 methylation might represent a novel strategy for developing new anti-invasive/anti-metastatic drugs. Moreover, methylated Twist1 (Arg-34), as such, could also emerge as a potential important biomarker for lung cancer.
引用
收藏
页码:13479 / 13489
页数:11
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