TEAD1 mediates the oncogenic activities of Hippo-YAP1 signaling in osteosarcoma
TEAD1 mediates the oncogenic activities of Hippo-YAP1 signaling in osteosarcoma
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DOI：
10.1016/j.bbrc.2017.05.032
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发表时间：
2017-06-24
影响因子：
3.1
通讯作者：
Guo, Fengbo
中科院分区：
文献类型：
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作者：
Chai, Jiwei;Xu, Shijie;Guo, Fengbo
Hippo信号通路是一个进化上保守的发育网络，调控下游转录共激活因子雅普和TAZ，它们结合并激活TEAD的输出，负责细胞增殖、凋亡和干细胞自我更新。新出现的证据已经显示了Hippo信号传导的肿瘤抑制特性。然而，关于骨肉瘤（OS）中Hippo通路下游转录因子的知识有限。在这项研究中，我们证明，TEAD 1是在OS的Hippo信号通路的主要转录因子。TEAD 1的基因沉默抑制OS细胞的多种恶性表型，包括细胞增殖，凋亡抵抗，和侵袭潜力。从机制上讲，我们发现TEAD 1在很大程度上对其功能靶点PTGS 2和CYR 61进行转录控制。总的来说，这项工作确定了YAP 1/TEAD 1复合物作为OS中Hippo信号转导的代表性失调概况，并提供了靶向TEAD 1可能是骨肉瘤治疗策略的原理证明。(C)2017由Elsevier Inc.出版
Hippo signaling pathway is an evolutionarily conserved developmental network that governs the downstream transcriptional co-activators, YAP and TAZ, which bind to and activate the output of TEADs that responsible for cell proliferation, apoptosis, and stem cell self renewal. Emerging evidence has shown the tumor suppressor properties of Hippo signaling. However, limited knowledge is available concerning the downstream transcription factors of Hippo pathway in osteosarcoma (OS). In this study, we demonstrated that TEAD1 was the major transcription factor of Hippo signaling pathway in OS. Genetic silencing of TEAD1 suppressed multiple malignant phenotypes of OS cells including cell proliferation, apoptosis resistance, and invasive potential. Mechanistically, we showed that TEAD1 largely exerted its transcriptional control of its functional targets, PTGS2 and CYR61. Collectively, this work identifies the YAP1/TEAD1 complex as the representative dysregulated profile of Hippo signaling in OS and provides proof-of-principle that targeting TEAD1 may be a therapeutic strategy of osteosarcoma. (C) 2017 Published by Elsevier Inc.