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MELK is an oncogenic kinase essential for metastasis,mitotic progression,and programmed death in lung carcinoma

查看全文 作　　者：Qin [1,2]Tang;Wan [1,2]Li;Xiangjin [1,2]Zheng;Liwen [1,2]Ren;Jinyi [1,2]Liu;Sha [1,2]Li;Jinhua [1,2]Wang;Guanhua [1,2]Du 高影响力作者 机构地区：[1]The State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Beijing,China and 2Key Laboratory of Drug Target Research and Drug Screen,Institute of Materia Medica,Chinese Academy of Medical Science;[2]Peking Union Medical College,100050 Beijing,China高影响力机构 出　　处：《Signal Transduction and Targeted Therapy》索引2020年第5卷第1期,共12页高影响力期刊 基　　金：supported by grants from the National Natural Science Foundation of China(81803584 for Qin Tang);China Postdoctoral Science Foundation(2018M640093 for Qin Tang);National Natural Science Foundation of China(81573454 for Jinhua Wang,81703536 for Wan Li);Beijing Natural Science Foundation(7172142);CAMS Innovation Fund for Medical Sciences(2016-I2M-3-007);Technology Major Projects for“Major New Drugs Innovation and Development”(2018ZX09711001-005-025 and 2018ZX09711001-012). 摘　　要：Lung cancer is the fastest growth rate of morbidity and mortality in nearly a decade,and remains difficult to treat.Furthermore,the molecular mechanisms underlying its development are still unclear.In this study,bioinformatics analysis showed that MELK was highly expressed in lung cancer and negatively correlated to the survival of lung adenocarcinoma(LUAD).Immunohistochemistry analysis of LUAD patient tissues revealed there were a high level of MELK expression in LUAD.Knockdown of MELK expression inhibits the migration and invasion of LUAD cells,which may be mediated by Twist1,Slug,MMP7,and N-catenin.Overexpression of MELK promoted the growth of LUAD cells in medium,3D Matrigel,and nude mice.Inhibition of MELK by OTSSP167 arrested cycle of LUAD cells at G2/M phase via PLK1-CDC25C-CDK1 pathway,and triggered apoptosis-mediated pyroptosis.Together,these data indicate that MELK is critical for metastasis,mitotic progression,and programmed death of LUAD and may be a promising therapeutic target for LUAD. 关 键 词：METASTASIS PLK1 LUNG
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