Hippo/YAP signaling pathway is involved in osteosarcoma chemoresistance  

作　　者：Dong-Yu Wang Ya-Nan Wu Jun-Qi Huang Wei Wang Meng Xu Jin-Peng Jia Gang Han Bei-Bei Mao Wen-Zhi Bi 

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

出　　处：《Chinese Journal of Cancer》2016年第7期366-373,共8页

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.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 

分 类 号：R738[医药卫生—肿瘤]