WIP Drives Tumor Progression through YAP/TAZ-Dependent Autonomous Cell Growth

In cancer, the deregulation of growth signaling pathways drives changes in the cell¿s architecture and its environment that allow autonomous growth of tumors. These cells then acquire a tumor-initiating ¿stemness¿ phenotype responsible for disease advancement to more aggressive stages. Here, we show...

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Autores: Gargini, Ricardo, Escoll, Maribel, García, Esther, García-Escudero, Ramón, Wandosell, Francisco, Antón, Inés María
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/152310
Acceso en línea:http://hdl.handle.net/10261/152310
Access Level:acceso abierto
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spelling WIP Drives Tumor Progression through YAP/TAZ-Dependent Autonomous Cell GrowthGargini, RicardoEscoll, MaribelGarcía, EstherGarcía-Escudero, RamónWandosell, FranciscoAntón, Inés MaríaIn cancer, the deregulation of growth signaling pathways drives changes in the cell¿s architecture and its environment that allow autonomous growth of tumors. These cells then acquire a tumor-initiating ¿stemness¿ phenotype responsible for disease advancement to more aggressive stages. Here, we show that high levels of the actin cytoskeleton-associated protein WIP (WASP-interacting protein) correlates with tumor growth, both of which are linked to the tumor-initiating cell phenotype. We find that WIP controls tumor growth by boosting signals that stabilize the YAP/TAZ complex via a mechanism mediated by the endocytic/endosomal system. When WIP levels are high, the ß-catenin Adenomatous polyposis coli (APC)-axin-GSK3 destruction complex is sequestered to the multi-vesicular body compartment, where its capacity to degrade YAP/TAZ is inhibited. YAP/TAZ stability is dependent on Rac, p21-activated kinase (PAK) and mammalian diaphanous-related formin (mDia), and is Hippo independent. This close biochemical relationship indicates an oncogenic role for WIP in the physiology of cancer pathology by increasing YAP/TAZ stability.MINECO (SAF2013-45937-R to I.M.A.) and MINECO/FEDER (SAF2015-70368-R to I.M.A. and F.W.), the European Union (EU-FP7-2009-CT222887 to F.W.), the Instituto de Salud Carlos III Centro de Investigación Biomédica en Red (CIBERNED to F.W.) and by a grant from ISCIII-RETIC (RD12/0036/0009 to R.G.E.)Peer ReviewedCell PressInstituto de Salud Carlos IIIMinisterio de Economía y Competitividad (España)European CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2017201720162017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/152310reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1523102026-05-22T06:33:51Z
dc.title.none.fl_str_mv WIP Drives Tumor Progression through YAP/TAZ-Dependent Autonomous Cell Growth
title WIP Drives Tumor Progression through YAP/TAZ-Dependent Autonomous Cell Growth
spellingShingle WIP Drives Tumor Progression through YAP/TAZ-Dependent Autonomous Cell Growth
Gargini, Ricardo
title_short WIP Drives Tumor Progression through YAP/TAZ-Dependent Autonomous Cell Growth
title_full WIP Drives Tumor Progression through YAP/TAZ-Dependent Autonomous Cell Growth
title_fullStr WIP Drives Tumor Progression through YAP/TAZ-Dependent Autonomous Cell Growth
title_full_unstemmed WIP Drives Tumor Progression through YAP/TAZ-Dependent Autonomous Cell Growth
title_sort WIP Drives Tumor Progression through YAP/TAZ-Dependent Autonomous Cell Growth
dc.creator.none.fl_str_mv Gargini, Ricardo
Escoll, Maribel
García, Esther
García-Escudero, Ramón
Wandosell, Francisco
Antón, Inés María
author Gargini, Ricardo
author_facet Gargini, Ricardo
Escoll, Maribel
García, Esther
García-Escudero, Ramón
Wandosell, Francisco
Antón, Inés María
author_role author
author2 Escoll, Maribel
García, Esther
García-Escudero, Ramón
Wandosell, Francisco
Antón, Inés María
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Ministerio de Economía y Competitividad (España)
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description In cancer, the deregulation of growth signaling pathways drives changes in the cell¿s architecture and its environment that allow autonomous growth of tumors. These cells then acquire a tumor-initiating ¿stemness¿ phenotype responsible for disease advancement to more aggressive stages. Here, we show that high levels of the actin cytoskeleton-associated protein WIP (WASP-interacting protein) correlates with tumor growth, both of which are linked to the tumor-initiating cell phenotype. We find that WIP controls tumor growth by boosting signals that stabilize the YAP/TAZ complex via a mechanism mediated by the endocytic/endosomal system. When WIP levels are high, the ß-catenin Adenomatous polyposis coli (APC)-axin-GSK3 destruction complex is sequestered to the multi-vesicular body compartment, where its capacity to degrade YAP/TAZ is inhibited. YAP/TAZ stability is dependent on Rac, p21-activated kinase (PAK) and mammalian diaphanous-related formin (mDia), and is Hippo independent. This close biochemical relationship indicates an oncogenic role for WIP in the physiology of cancer pathology by increasing YAP/TAZ stability.
publishDate 2016
dc.date.none.fl_str_mv 2016
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/152310
url http://hdl.handle.net/10261/152310
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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