Universität zu Köln

Shen, Ying, Wang, Xiaohong ORCID: 0000-0001-8628-243X, Liu, Yi, Singhal, Mahak ORCID: 0000-0002-7303-9585, Gurkaslar, Can ORCID: 0000-0002-3175-5671, Valls, Aida Freire, Lei, Yi, Hu, Wenjie, Schermann, Geza, Adler, Heike, Yu, Fa-Xing, Fischer, Tamas, Zhu, Yi, Augustin, Hellmut G., Schmidt, Thomas and de Almodovar, Carmen Ruiz (2021). STAT3-YAP/TAZ signaling in endothelial cells promotes tumor angiogenesis. Sci. Signal., 14 (712). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1937-9145

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Shen, Ying UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Xiaohong UNSPECIFIED orcid.org/0000-0001-8628-243X UNSPECIFIED Liu, Yi UNSPECIFIED UNSPECIFIED UNSPECIFIED Singhal, Mahak UNSPECIFIED orcid.org/0000-0002-7303-9585 UNSPECIFIED Gurkaslar, Can UNSPECIFIED orcid.org/0000-0002-3175-5671 UNSPECIFIED Valls, Aida Freire UNSPECIFIED UNSPECIFIED UNSPECIFIED Lei, Yi UNSPECIFIED UNSPECIFIED UNSPECIFIED Hu, Wenjie UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermann, Geza UNSPECIFIED UNSPECIFIED UNSPECIFIED Adler, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Yu, Fa-Xing UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Tamas UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhu, Yi UNSPECIFIED UNSPECIFIED UNSPECIFIED Augustin, Hellmut G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED de Almodovar, Carmen Ruiz UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-598418
DOI:	10.1126/scisignal.abj8393
Journal or Publication Title:	Sci. Signal.
Volume:	14
Number:	712
Date:	2021
Publisher:	AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication:	WASHINGTON
ISSN:	1937-9145
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NUCLEAR IMPORT; STAT3 ACTIVITY; YAP; YAP/TAZ; THERAPY; CANCER; ACTIVATOR; ROLES; LOCALIZATION; METASTASIS Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59841