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

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Item Type:	Article
Title:	The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/β-catenin signaling
Creators Name:	Birdsey, G.M., Shah, A.V., Dufton, N., Reynolds, L.E., Osuna Almagro, L., Yang, Y., Aspalter, I.M., Khan, S.T., Mason, J.C., Dejana, E., Göttgens, B., Hodivala-Dilke, K., Gerhardt, H., Adams, R.H. and Randi, A.M.
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/{beta}-catenin pathway by promoting {beta}-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 {beta}-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.
Keywords:	{beta} Catenin, Cadherins, CD Antigens, Chromatin Immunoprecipitation, Cultured Cells, Frizzled Receptors, Human Umbilical Vein Endothelial Cells, Integrases, Lung, Oncogene Proteins, Physiologic Neovascularization, Pregnancy, Real-Time Polymerase Chain Reaction, Signal Transduction, Transcription Factors, Transgenic Mice, Vascular Endothelial Growth Factor A, Vascular Endothelium, Western Blotting, Wnt Proteins, Animals, Mice
Source:	Developmental Cell
ISSN:	1534-5807
Publisher:	Cell Press / Elsevier
Volume:	32
Number:	1
Page Range:	82-96
Date:	12 January 2015
Official Publication:	https://doi.org/10.1016/j.devcel.2014.11.016
PubMed:	View item in PubMed

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