doi: 10.1186/s40880-016-0109-z
Hippo/YAP signaling pathway is involved in osteosarcoma chemoresistance
Dong-Yu Wang, Ya-Nan Wu, Jun-Qi Huang, Wei Wang, Meng Xu, Jin-Peng Jia, Gang Han, Bei-Bei Mao and Wen-Zhi Bi
Department of Orthopaedics and Rehabilitation, PLA General Hospital
[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.
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.
Chinese Journal of Cancer 2016, Volume: 35, Issue 7
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Dong-Yu Wang, Ya-Nan Wu, Jun-Qi Huang, Wei Wang, Meng Xu, Jin-Peng Jia, Gang Han, Bei-Bei Mao and Wen-Zhi Bi. Hippo/YAP signaling pathway is involved in osteosarcoma chemoresistance. Chin J Cancer. 2016, 35:47. doi:10.1186/s40880-016-0109-z
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[ Html full-text / Citation export] (BioMed Central)
[Google Scholar]
Cite this article
Dong-Yu Wang, Ya-Nan Wu, Jun-Qi Huang, Wei Wang, Meng Xu, Jin-Peng Jia, Gang Han, Bei-Bei Mao and Wen-Zhi Bi. Hippo/YAP signaling pathway is involved in osteosarcoma chemoresistance. Chin J Cancer. 2016, 35:47. doi:10.1186/s40880-016-0109-z
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