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Hippo/YAP signaling pathway is involved in osteosarcoma chemoresistance

查看全文 作  者:Dong-Yu [1]Wang;Ya-Nan [1]Wu;Jun-Qi [1]Huang;Wei [1]Wang;Meng [1]Xu;Jin-Peng [1]Jia;Gang [1]Han;Bei-Bei [2]Mao;Wen-Zhi [1]Bi 高影响力作者 机构地区:[1]Department of Orthopaedics and Rehabilitation,PLA General Hospital;[2]State Key Laboratory of Brain and Cognitive Sciences,Institute of Biophysics,Chinese Academy of Sciences高影响力机构 出  处:《Chinese Journal of Cancer》索引2016年第35卷第7期,共8页高影响力期刊 基  金:supported by the National Natural Science Foundation of China(No.81172553 and 81472513 to WB) 摘  要:Background:Osteosarcoma is the most common bone malignancy in children and adolescents,and 20%-30%of the patients suffer from poor prognosis because of individual chemoresistance.The Hippo/yes-associated protein(YAP) signaling pathway has been shown to play a role in tumor chemoresistance,but no previous report has focused on its involvement in osteosarcoma chemoresistance.This study aimed to investigate the role of the Hippo/YAP signaling pathway in osteosarcoma chemoresistance and to determine potential treatment targets.Methods:Using the Cell Titer-Glo Luminescent cell viability assay and flow cytometry analysis,we determined the proliferation and chemosensitivity of YAP-overexpressing and YAP-knockdown osteosarcoma cells.In addition,using western blotting and the real-time polymerase chain reaction technique,we investigated the alteration of the Hippo/YAP signaling pathway in osteosarcoma cells treated with chemotherapeutic agents.Results:Mammalian sterile 20-like kinase 1(MST1) degradation was increased,and large tumor suppressor kinase1/2(LAT51/2) total protein levels were decreased by methotrexate and doxorubicin,which increased activation and nuclear translocation of YAP.Moreover,YAP increased the proliferation and chemoresistance of MG63 cells.Conclusions:The Hippo/YAP signaling pathway plays a role in osteosarcoma chemoresistance,and YAP is a potential target for reducing chemoresistance. 关 键 词:肿瘤耐药 信号通路 骨肉瘤 河马 化疗 流式细胞仪分析 聚合酶链反应技术 信号转导通路
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