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Dev Cell. 2015 Jan 12;32(1):82-96. doi: 10.1016/j.devcel.2014.11.016.

The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/β-catenin signaling.

Author information

1
National Heart and Lung Institute (NHLI) Vascular Sciences, Hammersmith Hospital, Imperial College London, London W12 0NN, UK.
2
Centre for Tumour Biology, Barts Cancer Institute - a CR-UK Centre of Excellence, John Vane Science Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
3
Vascular Biology Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, UK.
4
FIRC Institute of Molecular Oncology Foundation, IFOM, 20139 Milan, Italy.
5
Department of Haematology, Wellcome Trust and MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
6
Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and Faculty of Medicine, University of Münster, D-48149 Münster, Germany.
7
National Heart and Lung Institute (NHLI) Vascular Sciences, Hammersmith Hospital, Imperial College London, London W12 0NN, UK. Electronic address: a.randi@imperial.ac.uk.

Abstract

Blood vessel stability is essential for embryonic development; in the adult, many diseases are associated with loss of vascular integrity. The ETS transcription factor ERG drives expression of VE-cadherin and controls junctional integrity. We show that constitutive endothelial deletion of ERG (Erg(cEC-KO)) in mice causes embryonic lethality with vascular defects. Inducible endothelial deletion of ERG (Erg(iEC-KO)) results in defective physiological and pathological angiogenesis in the postnatal retina and tumors, with decreased vascular stability. ERG controls the Wnt/β-catenin pathway by promoting β-catenin stability, through signals mediated by VE-cadherin and the Wnt receptor Frizzled-4. Wnt signaling is decreased in ERG-deficient endothelial cells; activation of Wnt signaling with lithium chloride, which stabilizes β-catenin levels, corrects vascular defects in Erg(cEC-KO) embryos. Finally, overexpression of ERG in vivo reduces permeability and increases stability of VEGF-induced blood vessels. These data demonstrate that ERG is an essential regulator of angiogenesis and vascular stability through Wnt signaling.

PMID:
25584796
PMCID:
PMC4292982
DOI:
10.1016/j.devcel.2014.11.016
[Indexed for MEDLINE]
Free PMC Article

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