期刊论文详细信息
Cancer Communications | |
Hippo/YAP signaling pathway is involved in osteosarcoma chemoresistance | |
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 | |
[2]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
【 预 览 】
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RO201904022297831ZK.pdf | 2531KB | download |