The role of transcriptional coactivator TAZ in gliomas.
The role of transcriptional coactivator TAZ in gliomas.
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DOI：
10.18632/oncotarget.12625
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发表时间：
2016-12-13
期刊：
影响因子：
--
通讯作者：
Jia Z
中科院分区：
文献类型：
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作者：
Li W;Dong S;Wei W;Wang G;Zhang A;Pu P;Jia Z
转录辅激活因子（TAZ）是Hippo信号通路的重要下游效应因子之一。本研究探讨了TAZ在胶质瘤发生中的潜在意义。TAZ表达在胶质瘤标本中被鉴定为上调，并且与肿瘤分级正相关。同时，随着肿瘤分级的升高，其在细胞核中的表达逐渐增强。敲低TAZ可抑制胶质瘤细胞的增殖、侵袭和促进凋亡。相反，TAZ的强制上调促进胶质瘤细胞的增殖，侵袭，并抑制体外细胞凋亡。TAZ敲除肿瘤细胞后，原位胶质母细胞瘤小鼠模型胶质瘤生长受到抑制，存活时间延长。Ki67、MMP-9、Cyclin D1、Bcl-2和C-myc的表达随TAZ浓度的升高而变化。当TAZ被抑制时，EMT（上皮-间质转化）的生物标志物波形蛋白和N-钙粘蛋白下调。使用免疫共沉淀法鉴定TAZ与TEAD 4结合。因此，我们的研究结果表明，TAZ在胶质瘤中过度表达，并在高级别胶质瘤中更多地转移到细胞核中。TAZ通过促进胶质瘤生长参与胶质瘤发生，并可能有利于EMT进展。这一结果表明，TAZ作为一个潜在的治疗胶质瘤的目标。
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.