The role of transcriptional coactivator TAZ in gliomas
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Weijie Li1,2,3,4,*, Shicai Dong1,2,3,4,*, Wei Wei1, Guangxiu Wang1,2,3,4, Anling Zhang1,2,3,4, Peiyu Pu1,2,3,4, Zhifan Jia1,2,3,4
1Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, P.R. China
2Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
3Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, P.R. China
4Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, P.R. China
*These authors have contributed equally to this work
Jia Zhifan, email: [email protected]
Keywords: glioma, Hippo pathway, TAZ, TEAD4, proliferation
Received: March 18, 2016 Accepted: September 25, 2016 Published: October 13, 2016
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.
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