Hippo/YAP signaling pathway is involved in osteosarcoma chemoresistance.
Chin J Cancer
; 35: 47, 2016 May 20.
Article
em En
| MEDLINE
| ID: mdl-27206784
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Neoplasias Ósseas
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Osteossarcoma
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Proteínas Serina-Treonina Quinases
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Resistencia a Medicamentos Antineoplásicos
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Proteínas Adaptadoras de Transdução de Sinal
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Antineoplásicos
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article