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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 723926.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
PTEN mediates Notch-dependent stalk cell arrest in angiogenesis
Authors:Serra, H.; Chivite, I.; Angulo-Urarte, A.; Soler, A.; Sutherland, J. D.; Arruabarrena-Aristorena, A.; Ragab, A.; Lim, R.; Malumbres, M.; Fruttiger, M.; Potente, M.; Serrano, M.; Fabra, A.; Vinals, F.; Casanovas, O.; Pandolfi, P. P.; Bigas, A.; Carracedo, A.; Gerhardt, H.; Graupera, M.
Date of Publication (YYYY-MM-DD):2015
Title of Journal:Nat Commun
Volume:6
Start Page:7935
Audience:Not Specified
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:CIC-bioGUNE, Technology Park of Bizkaia, 48160 Derio, Bizkaia, Spain. Vascular Biology Laboratory, London Research Institute-Cancer Research UK, London WC2A 3LY, UK. Max Planck Institute for Heart and Lung Research, D61231 Bad Nauheim, Germany. Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain. UCL Institute of Ophthalmology, University Collage of London, London EC1V9EL, UK. Centre d'Oncologia Molecular, IDIBELL, Universitat de Barcelona, 08907 L'Hospitalet de Llobregat, Barcelona. 1] Translation Research Laboratory, Catalan Institute of Oncology, IDIBELL, Universitat de Barcelona, 08907 L'Hospitalet de Llobregat, Barcelona, Spain [2] Departament de Ciencies Fisiologiques II, Universitat de Barcelona, 08907 L'Hospitalet de Llobregat, Spain. Translation Research Laboratory, Catalan Institute of Oncology, IDIBELL, Universitat de Barcelona, 08907 L'Hospitalet de Llobregat, Barcelona, Spain. Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA. Program in Cancer Research, Hospital del Mar Medical Research Institute (IMIM), Barcelona Biomedical Research Park, 08003 Barcelona, Spain. 1] CIC-bioGUNE, Technology Park of Bizkaia, 48160 Derio, Bizkaia, Spain [2] IKERBASQUE, Basque Foundation of Science, 48011 Bilbao, Bizkaia, Spain [3] Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), Bilbao 48940, Spain. 1] Vascular Biology Laboratory, London Research Institute-Cancer Research UK, London WC2A 3LY, UK [2] Max-Delbrueck Center for Molecular Medicine (MDC), Robert-Rossle-Strasse 10, Berlin 13125, Germany. %W NLM %G eng
Identifiers:ISSN:2041-1723 %R 10.1038/ncomms8935

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