PRMT1 Is a Novel Regulator of Epithelial-Mesenchymal-Transition in Non-small Cell Lung Cancer.
PRMT1 Is a Novel Regulator of Epithelial-Mesenchymal-Transition in Non-small Cell Lung Cancer.
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DOI：
10.1074/jbc.m114.636050
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发表时间：
2015-05-22
期刊：
影响因子：
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通讯作者：
Bikkavilli RK
中科院分区：
文献类型：
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作者：
Avasarala S;Van Scoyk M;Karuppusamy Rathinam MK;Zerayesus S;Zhao X;Zhang W;Pergande MR;Borgia JA;DeGregori J;Port JD;Winn RA;Bikkavilli RK
背景：PRMT 1在肺癌中表达上调。结果：PRMT 1是EMT的新调控因子，Twist 1是PRMT 1的新底物。结论：Twist 1的PRMT 1甲基化是E-cadherin抑制活性所必需的。意义：靶向PRMT 1介导的Twist 1甲基化可能代表了开发新的抗侵袭/抗转移药物的新策略。蛋白质精氨酸甲基转移酶1（PRMT 1）在癌症中被上调，对癌细胞增殖很重要。然而，PRMT 1在肺癌进展和转移中的作用仍不完全清楚。在本研究中，我们表明PRMT 1是上皮-间质转化（EMT），癌细胞迁移和侵袭的重要调节因子，这些都是癌症进展和转移过程中的重要过程。此外，我们已经确定Twist 1，一个基本的螺旋-环-螺旋转录因子和一个众所周知的E-钙粘蛋白阻遏物，作为一种新的PRMT 1底物。两者合计，我们表明，PRMT 1是一种新的调节EMT和精氨酸34（Arg-34）甲基化的Twist 1作为一个独特的“甲基精氨酸标记”的积极E-钙粘蛋白的镇压。因此，靶向PRMT 1介导的Twist 1甲基化可能代表了开发新的抗侵袭/抗转移药物的新策略。此外，甲基化Twist 1（Arg-34）本身也可能成为肺癌的潜在重要生物标志物。
Background: PRMT1 is up-regulated in lung cancer. Results: PRMT1 is a novel regulator of EMT and Twist1 is a new PRMT1 substrate. Conclusion: PRMT1-methylation of Twist1 is required for active E-cadherin repression. Significance: Targeting PRMT1-mediated Twist1 methylation might represent a novel strategy for developing new anti-invasive/anti-metastatic drugs. 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.