2024-03-29T11:57:35Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/100082023-10-06T12:12:29Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
Repisalud
author
Serra, Helena
author
Chivite, Iñigo
author
Angulo-Urarte, Ana
author
Soler, Adriana
author
Sutherland, James D
author
Arruabarrena-Aristorena, Amaia
author
Ragab, Anan
author
Lim, Radiance
author
Malumbres Martinez, Marcos
author
Fruttiger, Marcus
author
Potente, Michael
author
Serrano Marugan, Manuel
author
Fabra, Àngels
author
Viñals, Francesc
author
Casanovas, Oriol
author
Pandolfi, Pier Paolo
author
Bigas, Anna
author
Carracedo, Arkaitz
author
Gerhardt, Holger
author
Graupera, Mariona
funder
Unión Europea
funder
Institut d Investigació Biomédica de Bellvitge
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Instituto de Salud Carlos III
funder
Cancer Research UK (Reino Unido)
funder
Ministerio de Economía y Competitividad (España)
funder
Basque Government (España)
2020-05-08T17:47:53Z
2020-05-08T17:47:53Z
2015-07-31
Nat Commun. 2015;6:7935
2041-1723
http://hdl.handle.net/20.500.12105/10008
26228240
10.1038/ncomms8935
2041-1723
Nature communications
Coordinated activity of VEGF and Notch signals guides the endothelial cell (EC) specification into tip and stalk cells during angiogenesis. Notch activation in stalk cells leads to proliferation arrest via an unknown mechanism. By using gain- and loss-of-function gene-targeting approaches, here we show that PTEN is crucial for blocking stalk cell proliferation downstream of Notch, and this is critical for mouse vessel development. Endothelial deletion of PTEN results in vascular hyperplasia due to a failure to mediate Notch-induced proliferation arrest. Conversely, overexpression of PTEN reduces vascular density and abrogates the increase in EC proliferation induced by Notch blockade. PTEN is a lipid/protein phosphatase that also has nuclear phosphatase-independent functions. We show that both the catalytic and non-catalytic APC/C-Fzr1/Cdh1-mediated activities of PTEN are required for stalk cells' proliferative arrest. These findings define a Notch-PTEN signalling axis as an orchestrator of vessel density and implicate the PTEN-APC/C-Fzr1/Cdh1 hub in angiogenesis.
eng
PTEN mediates Notch-dependent stalk cell arrest in angiogenesis
journal article
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URL
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