PTEN mediates Notch-dependent stalk cell arrest in angiogenesis

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 s...

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Autores: Serra, Helena, Chivite, Iñigo, Angulo-Urarte, Ana, Soler, Adriana, Sutherland, James D, Arruabarrena-Aristorena, Amaia, Ragab, Anan, Lim, Radiance, Malumbres Martinez, Marcos, Fruttiger, Marcus, Potente, Michael, Serrano Marugan, Manuel, Fabra, Àngels, Viñals, Francesc, Casanovas, Oriol, Pandolfi, Pier Paolo, Bigas, Anna, Carracedo, Arkaitz, Gerhardt, Holger, Graupera, Mariona
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/10008
Acceso en línea:http://hdl.handle.net/20.500.12105/10008
Access Level:acceso abierto
Palabra clave:Anaphase-Promoting Complex-Cyclosome
Animals
Cdh1 Proteins
Cell Proliferation
Endothelial Cells
Fluorescent Antibody Technique
Immunoblotting
Mice
Neovascularization, Physiologic
PTEN Phosphohydrolase
Polymerase Chain Reaction
RNA, Messenger
Receptors, Notch
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network_acronym_str ES
network_name_str España
repository_id_str
spelling PTEN mediates Notch-dependent stalk cell arrest in angiogenesisSerra, HelenaChivite, IñigoAngulo-Urarte, AnaSoler, AdrianaSutherland, James DArruabarrena-Aristorena, AmaiaRagab, AnanLim, RadianceMalumbres Martinez, MarcosFruttiger, MarcusPotente, MichaelSerrano Marugan, ManuelFabra, ÀngelsViñals, FrancescCasanovas, OriolPandolfi, Pier PaoloBigas, AnnaCarracedo, ArkaitzGerhardt, HolgerGraupera, MarionaAnaphase-Promoting Complex-CyclosomeAnimalsCdh1 ProteinsCell ProliferationEndothelial CellsFluorescent Antibody TechniqueImmunoblottingMiceNeovascularization, PhysiologicPTEN PhosphohydrolasePolymerase Chain ReactionRNA, MessengerReceptors, NotchCoordinated 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.Unión EuropeaInstitut d Investigació Biomédica de BellvitgeUnión Europea. Comisión Europea. European Research Council (ERC)Instituto de Salud Carlos IIICancer Research UK (Reino Unido)Ministerio de Economía y Competitividad (España)Basque Government (España)20202020-05-0820152015-07-3120152015-07-31journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/20.500.12105/10008reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/100082026-06-12T12:43:37Z
dc.title.none.fl_str_mv PTEN mediates Notch-dependent stalk cell arrest in angiogenesis
title PTEN mediates Notch-dependent stalk cell arrest in angiogenesis
spellingShingle PTEN mediates Notch-dependent stalk cell arrest in angiogenesis
Serra, Helena
Anaphase-Promoting Complex-Cyclosome
Animals
Cdh1 Proteins
Cell Proliferation
Endothelial Cells
Fluorescent Antibody Technique
Immunoblotting
Mice
Neovascularization, Physiologic
PTEN Phosphohydrolase
Polymerase Chain Reaction
RNA, Messenger
Receptors, Notch
title_short PTEN mediates Notch-dependent stalk cell arrest in angiogenesis
title_full PTEN mediates Notch-dependent stalk cell arrest in angiogenesis
title_fullStr PTEN mediates Notch-dependent stalk cell arrest in angiogenesis
title_full_unstemmed PTEN mediates Notch-dependent stalk cell arrest in angiogenesis
title_sort PTEN mediates Notch-dependent stalk cell arrest in angiogenesis
dc.creator.none.fl_str_mv Serra, Helena
Chivite, Iñigo
Angulo-Urarte, Ana
Soler, Adriana
Sutherland, James D
Arruabarrena-Aristorena, Amaia
Ragab, Anan
Lim, Radiance
Malumbres Martinez, Marcos
Fruttiger, Marcus
Potente, Michael
Serrano Marugan, Manuel
Fabra, Àngels
Viñals, Francesc
Casanovas, Oriol
Pandolfi, Pier Paolo
Bigas, Anna
Carracedo, Arkaitz
Gerhardt, Holger
Graupera, Mariona
author Serra, Helena
author_facet Serra, Helena
Chivite, Iñigo
Angulo-Urarte, Ana
Soler, Adriana
Sutherland, James D
Arruabarrena-Aristorena, Amaia
Ragab, Anan
Lim, Radiance
Malumbres Martinez, Marcos
Fruttiger, Marcus
Potente, Michael
Serrano Marugan, Manuel
Fabra, Àngels
Viñals, Francesc
Casanovas, Oriol
Pandolfi, Pier Paolo
Bigas, Anna
Carracedo, Arkaitz
Gerhardt, Holger
Graupera, Mariona
author_role author
author2 Chivite, Iñigo
Angulo-Urarte, Ana
Soler, Adriana
Sutherland, James D
Arruabarrena-Aristorena, Amaia
Ragab, Anan
Lim, Radiance
Malumbres Martinez, Marcos
Fruttiger, Marcus
Potente, Michael
Serrano Marugan, Manuel
Fabra, Àngels
Viñals, Francesc
Casanovas, Oriol
Pandolfi, Pier Paolo
Bigas, Anna
Carracedo, Arkaitz
Gerhardt, Holger
Graupera, Mariona
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Unión Europea
Institut d Investigació Biomédica de Bellvitge
Unión Europea. Comisión Europea. European Research Council (ERC)
Instituto de Salud Carlos III
Cancer Research UK (Reino Unido)
Ministerio de Economía y Competitividad (España)
Basque Government (España)
dc.subject.none.fl_str_mv Anaphase-Promoting Complex-Cyclosome
Animals
Cdh1 Proteins
Cell Proliferation
Endothelial Cells
Fluorescent Antibody Technique
Immunoblotting
Mice
Neovascularization, Physiologic
PTEN Phosphohydrolase
Polymerase Chain Reaction
RNA, Messenger
Receptors, Notch
topic Anaphase-Promoting Complex-Cyclosome
Animals
Cdh1 Proteins
Cell Proliferation
Endothelial Cells
Fluorescent Antibody Technique
Immunoblotting
Mice
Neovascularization, Physiologic
PTEN Phosphohydrolase
Polymerase Chain Reaction
RNA, Messenger
Receptors, Notch
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.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-07-31
2015
2015-07-31
2020
2020-05-08
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/10008
url http://hdl.handle.net/20.500.12105/10008
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406470469058560
score 15,81155

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