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
Shao−Yao Ying,Xiaohong Wang,Yi Liu,Mahak Singhal,Can Gürkaşlar,Aïda Valls,Yi Lee,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)
被引量:52
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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