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PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism

引用

Acta Pharmaceutica Sinica B 2023年第1期13卷 157-173页

作者： Mingming Sun Leilei Li Yujia Niu Yingzhi Wang Qi Yan Fei Xie Yaya Qiao Jiaqi Song Huanran Sun Zhen Li Sizhen Lai Hongkai Chang Han Zhang Jiyan Wang Chenxin Yang Huifang Zhao Junzhen Tan Yanping Li Shuangping Liu Bin Lu Min Liu Guangyao Kong Yujun Zhao Chunze Zhang Shu-Hai Lin Cheng Luo Shuai Zhang Changliang Shan State Key Laboratory of Medicinal Chemical Biology College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjin 300350China Biomedical Translational Research Institute Jinan UniversityGuangzhou 510632China State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signaling NetworkSchool of Life SciencesXiamen UniversityXiamen 361102China School of Integrative Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Pathology and Institute of Precision Medicine Jining Medical UniversityJining 272067China Department of Pathology Medical SchoolDalian UniversityDalian 116622China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesHengyang Medical SchoolUniversity of South ChinaHengyang 421001China School of Laboratory Medicine and Life Sciences Wenzhou Medical UniversityWenzhou 325035China Institute of Biomedical Sciences Shandong Provincial Key Laboratory of Animal Resistance BiologyCollaborative Innovation Center of Cell Biology in Universities of ShandongCollege of Life SciencesShandong Normal UniversityJinan 250014China National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy the Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710004China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Colorectal Surgery Tianjin Union Medical Center Nankai UniversityTianjin 300121China

Metabolic reprogramming is a hallmark of cancer,including lung ***,the exact underlying mechanism and therapeutic potential are largely *** we report that protein arginine methyltransferase 6(PRMT6)is highly expressed in lung cancer and is required for cell metabolism,tumorigenicity,and cisplatin response of lung ***6 regulated the oxidative pentose phosphate pathway(PPP)flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phosphogluconate dehydrogenase(6PGD)and a-enolase(ENO1).Furthermore,PRMT6 methylated R324 of 6PGD to enhancing its activity;while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate(2-PG)binding to ENO1,***,targeting PRMT6 blocked the oxidative PPP flux,glycolysis pathway,and tumor growth,as well as enhanced the antitumor effects of cisplatin in lung ***,this study demonstrates that PRMT6 acts as a posttranslational modification(PTM)regulator of glucose metabolism,which leads to the pathogenesis of lung *** was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

关键词： Lung cancer Metabolic reprogramming Post-translational modification PRMT6 pentose phosphate pathway flux Glycolysis 6-Phospho-gluconate dehydrogenase a-enolase ENO1

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