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Title: PTEN mediates Notch-dependent stalk cell arrest in angiogenesis.
Author: Serra, Helena
Chivite, Íñigo
Angulo Aguado, Ana
Soler, Adriana
Sutherland, James David
Arruabarrena-Aristorena, Amaia
Ragab, Anan
Lim, Radiance
Malumbres, Marcos
Fruttiger, Marcus
Potente, Michael
Serrano, Manuel
Fabra Fres, Àngels
Viñals Canals, Francesc
Casanovas i Casanovas, Oriol
Pandolfi, Pier Paolo
Bigas Salvans, Anna
Carracedo, Arkaitz
Gerhardt, Holger
Graupera i Garcia-Milà, Mariona
Keywords: Angiogènesi
Proliferació cel·lular
Cell proliferation
Issue Date: 31-Jul-2015
Publisher: Nature Publishing Group
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Nature Communications, 2015, vol. 6, p. 7935
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ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Publicacions de projectes de recerca finançats per la UE

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