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.
Dong-Yu WangYa-Nan WuJun-Qi HuangWei WangMeng XuJin-Peng JiaGang HanBei-Bei MaoWen-Zhi Bi
