Hippo/YAP signaling pathway is involved in osteosarcoma chemoresistance

Cancer Communications

Ya-Nan Wu¹  Jun-Qi Huang¹  Wen-Zhi Bi¹  Gang Han¹  Meng Xu¹  Wei Wang¹  Dong-Yu Wang¹  Jin-Peng Jia¹  Bei-Bei Mao² 

[1] Department of Orthopaedics and Rehabilitation, PLA General Hospital, Beijing, P. R. China;State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, P. R. China

关键词: Hippo;    YAP;    Methotrexate;    Doxorubicin;    Osteosarcoma;    Chemoresistance;   

DOI  :  10.1186/s40880-016-0109-z

学科分类：肿瘤学

来源: Springer

【 摘 要 】

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. 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. 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. The Hippo/YAP signaling pathway plays a role in osteosarcoma chemoresistance, and YAP is a potential target for reducing chemoresistance.

【 授权许可】

CC BY