Hippo/YAP signaling pathway is involved in osteosarcoma chemoresistance.

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.

• Authors: Dong-Yu Wang, Ya-Nan Wu, Jun-Qi Huang, Wei Wang, Meng Xu, Jin-Peng Jia, Gang Han, Bei-Bei Mao, Wen-Zhi Bi
• Journal: Chinese journal of cancer (Chin J Cancer) Vol. 35 Pg. 47 (May 20 2016) ISSN: 1944-446X [Electronic] England
• PMID: 27206784 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Antineoplastic Agents
• Phosphoproteins
• Transcription Factors
• YAP-Signaling Proteins
• YAP1 protein, human
• Doxorubicin
• Protein Serine-Threonine Kinases
• Methotrexate

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Antineoplastic Agents (pharmacology)
• Bone Neoplasms (genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm
• Gene Expression Regulation, Neoplastic (drug effects)
• Hippo Signaling Pathway
• Humans
• Methotrexate (pharmacology)
• Osteosarcoma (genetics, metabolism)
• Phosphoproteins (genetics, metabolism)
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Signal Transduction (drug effects)
• Transcription Factors
• YAP-Signaling Proteins