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 sign?aling pathway in osteosarcoma chemoresistance and to determine potential treatment targets.
Methods:Using the Cell Titer?Glo Luminescent cell viability assay and lfow 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 kinase 1/2 (LATS1/2) 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.