Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-03278-w
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Funding
- Canadian Institute of Health Research (CIHR) [119325, 148629]
- Canadian Breast Cancer Foundation (CBCF)
- Roswell Park Cancer Institute
- National Cancer Institute (NCI) [P30 CA016056, R01 CA207504]
- Roswell Park Alliance Foundation
- American Cancer Society Research Scholar [RSG-14-214-01-TBE]
- Vanier Canada Graduate Scholarship
- Ontario International Graduate Scholarship
- Queen Elizabeth II Graduate Scholarship in Science and Technology
- NATIONAL CANCER INSTITUTE [R35CA196878, R21CA179693, P30CA016056, R01CA207504] Funding Source: NIH RePORTER
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The Hippo pathway is a central regulator of tissue development and homeostasis, and has been reported to have a role during vascular development. Here we develop a bioluminescence-based biosensor that monitors the activity of the Hippo core component LATS kinase. Using this biosensor and a library of small molecule kinase inhibitors, we perform a screen for kinases modulating LATS activity and identify VEGFR as an upstream regulator of the Hippo pathway. We find that VEGFR activation by VEGF triggers PI3K/MAPK signaling, which subsequently inhibits LATS and activates the Hippo effectors YAP and TAZ. We further show that the Hippo pathway is a critical mediator of VEGF-induced angiogenesis and tumor vasculogenic mimicry. Thus, our work offers a biosensor tool for the study of the Hippo pathway and suggests a role for Hippo signaling in regulating blood vessel formation in physiological and pathological settings.
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