血管生成
河马信号通路
癌症研究
车站3
细胞生物学
肿瘤进展
生物
血管内皮生长因子
STAT蛋白
信号转导
癌症
血管内皮生长因子受体
遗传学
作者
Ying Shen,Xiaohong Wang,Yi Liu,Mahak Singhal,Can Gürkaşlar,Aı̈da Valls,Lei Yi,Wenjie Hu,Géza Schermann,Heike Adler,Fa‐Xing Yu,Tamás Fischer,Yi Zhu,Hellmut G. Augustin,Thomas Schmidt,Carmen Ruiz de Almodóvar
出处
期刊:Science Signaling
[American Association for the Advancement of Science (AAAS)]
日期:2021-12-07
卷期号:14 (712): eabj8393-eabj8393
被引量:115
标识
DOI:10.1126/scisignal.abj8393
摘要
The nuclear translocation and activity of the cotranscriptional activators YAP and TAZ (YAP/TAZ) in endothelial cells (ECs) are crucial during developmental angiogenesis. Here, we studied the role of YAP/TAZ signaling in ECs in tumor angiogenesis and found that the expression of YAP/TAZ and downstream target genes in ECs correlated with tumor vascularization in human colorectal carcinomas and skin melanoma. Treatment with the YAP/TAZ inhibitor verteporfin reduced vessel density and tumor progression in a mouse colorectal cancer (CRC) model. Conditional deletion of YAP/TAZ in ECs reduced tumor angiogenesis and growth in a mouse B16-F10 melanoma model. Using cultured ECs and mice with EC-specific ablation, we showed that signal transducer and activator of transcription 3 (STAT3) was required for the activation of YAP/TAZ in tumor-associated ECs. Moreover, we showed that STAT3-mediated signaling promoted YAP/TAZ activity and that the nuclear shuttling machinery for STAT3 was also required for YAP/TAZ nuclear translocation. Together, our data highlight the role of YAP/TAZ as critical players in ECs during tumor angiogenesis and provide insight into the signaling pathways leading to their activation.
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