title: 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.affiliation: Department of Orthopaedics and Rehabilitation, PLA General Hospital, Fuxing Rd 28, Beijing, 100853, P. R. China.
authors.forename: Dong-Yu
authors.initials: DY
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics and Rehabilitation, PLA General Hospital, Fuxing Rd 28, Beijing, 100853, P. R. China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics and Rehabilitation, PLA General Hospital, Fuxing Rd 28, Beijing, 100853, P. R. China.
authors.forename: Jun-Qi
authors.initials: JQ
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics and Rehabilitation, PLA General Hospital, Fuxing Rd 28, Beijing, 100853, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics and Rehabilitation, PLA General Hospital, Fuxing Rd 28, Beijing, 100853, P. R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics and Rehabilitation, PLA General Hospital, Fuxing Rd 28, Beijing, 100853, P. R. China.
authors.forename: Jin-Peng
authors.initials: JP
authors.lastname: Jia
authors.affiliation: Department of Orthopaedics and Rehabilitation, PLA General Hospital, Fuxing Rd 28, Beijing, 100853, P. R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Han
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, P. R. China.
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Mao
authors.affiliation: Department of Orthopaedics and Rehabilitation, PLA General Hospital, Fuxing Rd 28, Beijing, 100853, P. R. China. biwenzhi@sina.com.
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Bi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D000090683:Hippo Signaling Pathway; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D004317:Doxorubicin; D017346:Protein Serine-Threonine Kinases; D008727:Methotrexate
keywords: Chemoresistance; Doxorubicin; Hippo; Methotrexate; Osteosarcoma; YAP