STAT3-YAP/TAZ signaling in endothelial cells promotes tumor angiogenesis

Ying Shen, Xiaohong Wang*, Yi Liu, Mahak Singhal, Can Gürkaşlar, Aida Freire Valls, Yi Lei, Wenjie Hu, Géza Schermann, Heike Adler, Fa Xing Yu, Tamás Fischer, Yi Zhu, Hellmut G. Augustin, Thomas Schmidt*, Carmen Ruiz De Almodóvar*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    54 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Article numberabj8393
    JournalScience Signaling
    Volume14
    Issue number712
    DOIs
    Publication statusPublished - 7 Dec 2021

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