Hippo/YAP signaling pathway is involved in osteosarcoma chemoresistance. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Wang, Dong-Yu; Wu, Ya-Nan; Huang, Jun-Qi; Wang, Wei; Xu, Meng; Jia, Jin-Peng; Han, Gang; Mao, Bei-Bei; Bi, Wen-Zhi
• Is Part Of: Chinese journal of cancer. Volume 35:Issue 1(2016)
• Page Start: 1
• Page End: 8
• Publication Date: 2016-12
• Subjects: Hippo -- YAP -- Methotrexate -- Doxorubicin -- Osteosarcoma -- Chemoresistance; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s40880-016-0109-z
• Languages: English
• ISSNs: 1944-446X

Abstract

Abstract 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 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.