Phosphorylation of PHF2 by AMPK releases the repressive H3K9me2 and inhibits cancer metastasis
文献类型：期刊论文
| 作者 | Dong, Ying6,7; Hu, Hao7; Zhang, Xuan6,7 ; Zhang, Yunkai6,7; Sun, Xin7,9; Wang, Hanlin7,8; Kan, Weijuan7; Tan, Minjia6,7; Shi, Hong5; Zang, Yi3,4,7
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| 刊名 | Signal Transduction and Targeted Therapy
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| 出版日期 | 2023-03-06 |
| 卷号 | 8期号:4页码:1857-1873 |
| ISSN号 | 2095-9907 |
| DOI | 10.1038/s41392-022-01302-6 |
| 文献子类 | Article |
| 英文摘要 | Epithelial to mesenchymal transition (EMT) plays a crucial role in cancer metastasis, accompanied with vast epigenetic changes. AMP-activated protein kinase (AMPK), a cellular energy sensor, plays regulatory roles in multiple biological processes. Although a few studies have shed light on AMPK regulating cancer metastasis, the inside epigenetic mechanisms remain unknown. Herein we show that AMPK activation by metformin relieves the repressive H3K9me2-mediated silencing of epithelial genes (e.g., CDH1) during EMT processes and inhibits lung cancer metastasis. PHF2, a H3K9me2 demethylase, was identified to interact with AMPKalpha2. Genetic deletion of PHF2 aggravates lung cancer metastasis and abolishes the H3K9me2 downregulation and anti-metastasis effect of metformin. Mechanistically, AMPK phosphorylates PHF2 at S655 site, enhancing PHF2 demethylation activity and triggering the transcription of CDH1. Furthermore, the PHF2-S655E mutant that mimics AMPK-mediated phosphorylation status further reduces H3K9me2 and suppresses lung cancer metastasis, while PHF2-S655A mutant presents opposite phenotype and reverses the anti-metastasis effect of metformin. PHF2-S655 phosphorylation strikingly reduces in lung cancer patients and the higher phosphorylation level predicts better survival. Altogether, we reveal the mechanism of AMPK inhibiting lung cancer metastasis via PHF2 mediated H3K9me2 demethylation, thereby promoting the clinical application of metformin and highlighting PHF2 as the potential epigenetic target in cancer metastasis. |
| 语种 | 英语 |
| CSCD记录号 | CSCD:7454536 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309631]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Shi, Hong; Zang, Yi; Li, Jia |
| 作者单位 | 1.Open Studio for Druggability Research of Marine Natural Products, Pilot National Laboratory for Marine Science and Technology (Qingdao), 1 Wenhai Road, Aoshanwei, Jimo, Qingdao 266237, China 2.Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China; 3.School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; 4.Lingang laboratory, Shanghai 201203, China; 5.Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China; 6.University of Chinese Academy of Sciences, Beijing 100049, China; 7.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; 8.Department of Pharmacology, Fudan University, Shanghai 201203, China; 9.School of Pharmacy, Henan University, Kaifeng 475004, China; |
| 推荐引用方式 GB/T 7714 | Dong, Ying,Hu, Hao,Zhang, Xuan,et al. Phosphorylation of PHF2 by AMPK releases the repressive H3K9me2 and inhibits cancer metastasis[J]. Signal Transduction and Targeted Therapy,2023,8(4):1857-1873. |
| APA | Dong, Ying.,Hu, Hao.,Zhang, Xuan.,Zhang, Yunkai.,Sun, Xin.,...&Li, Jia.(2023).Phosphorylation of PHF2 by AMPK releases the repressive H3K9me2 and inhibits cancer metastasis.Signal Transduction and Targeted Therapy,8(4),1857-1873. |
| MLA | Dong, Ying,et al."Phosphorylation of PHF2 by AMPK releases the repressive H3K9me2 and inhibits cancer metastasis".Signal Transduction and Targeted Therapy 8.4(2023):1857-1873. |
入库方式： OAI收割
来源：上海药物研究所
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