title: The role of transcriptional coactivator TAZ in gliomas.
abstract: The transcriptional coactivator with PDZ-binding motif (TAZ) is one of the important downstream effectors of Hippo pathway. In this study, the potential implication of TAZ in gliomagenesis was explored. TAZ expression was identified to be upregulated in glioma specimens and positively correlated with tumor grade. Meanwhile, its expression in nucleus was increased more significantly with the ascending order of tumor grade. Knocking down TAZ inhibited glioma cell proliferation, invasion and promoted apoptosis. Conversely, enforced upregulation of TAZ promoted proliferation, invasion of glioma cells, and suppressed apoptosis in vitro. When orthotopic glioblastoma mouse model implanted with TAZ knocked down cells, glioma growth was inhibited and survival period was prolonged. Expression of Ki67, MMP-9, Cyclin D1, Bcl-2 and C-myc was varied in accordance with the level of TAZ in glioma cell. The biomarkers of EMT (epithelial-mesenchymal transition), vimentin and N-cadherin, were downregulated when TAZ was suppressed. Using Co-immunoprecipitation TAZ was identified to bind to TEAD4. Therefore, our findings indicate that TAZ is overexpressed in glioma and translocated more into nucleus in high grade glioma. TAZ is involved in gliomagenesis by promoting glioma growth and may benefit to EMT progression. This result suggests that TAZ serves as a potential target for the treatment of glioma.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, P.R. China.|Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, P.R. China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, P.R. China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, P.R. China.|Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, P.R. China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, P.R. China.
authors.forename: Shicai
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, P.R. China.|Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, P.R. China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, P.R. China.
authors.forename: Guangxiu
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, P.R. China.|Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, P.R. China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, P.R. China.
authors.forename: Anling
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, P.R. China.|Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, P.R. China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, P.R. China.
authors.forename: Peiyu
authors.initials: P
authors.lastname: Pu
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, P.R. China.|Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, P.R. China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, P.R. China.
authors.forename: Zhifan
authors.initials: Z
authors.lastname: Jia
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D000091262:TEA Domain Transcription Factors; D013997:Time Factors; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: C000595707:BCL2 protein, human; D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; C489427:MYC protein, human; D009124:Muscle Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D000091262:TEA Domain Transcription Factors; C486309:TEAD4 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D019938:Cyclin D1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Hippo pathway; TAZ; TEAD4; glioma; proliferation