Cancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathway

Autores
Gargini, Ricardo; Cerliani, Juan Pablo; Escoll, Maribel; Anton, Ines M.; Wandosell, Francisco
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Many solid tumors contain a subpopulation of cells with stem characteristics and these are known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). These cells drive tumor growth and appear to be regulated by molecular pathway different from other cells in the tumor bulk. Here, we set out to determine whether elements of the PI3K-AKT pathway are necessary to maintain the CSC-like phenotype in breast tumor cells and for these cells to survive, bearing in mind that the identification of such elements is likely to be relevant to define future therapeutic targets. Our results demonstrate a close relationship between the maintenance of the CSC-like phenotype and the survival of these TICs. Inhibiting PI3K activity, or eliminating AKT activity, mostly that of the AKT1 isoform, produces a clear drop in TICs survival, and a reduction in the generation and growth of CD44(High) /CD24(Low) mammospheres. Surprisingly, the apoptosis of these TICs that is triggered by AKT1 deficiency is also associated with a loss of the stem cell/mesenchymal phenotype and a recovery of epithelial-like markers. Finally, we define downstream effectors that are responsible for controlling the CSC-phenotype, such as FoxO-Bim, and the death of these cells in the absence of AKT1. In summary, these data closely link the maintenance of the stem cell-like phenotype and the survival of these cells to the AKT-FoxO-Bim pathway.
Fil: Gargini, Ricardo. Universidad Autonoma de Madrid. Centro de Biologia Molecular; España
Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Escoll, Maribel. Universidad Autonoma de Madrid. Centro de Biologia Molecular; España. Consejo Superior de Investigaciones Cientificas. Centro Nacional de Biotecnologia; España
Fil: Anton, Ines M.. Consejo Superior de Investigaciones Cientificas. Centro Nacional de Biotecnologia; España. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas; España
Fil: Wandosell, Francisco. Universidad Autonoma de Madrid. Centro de Biologia Molecular; España
Materia
Stem Cells
Akt
Foxo
Bim
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/4625
Acceder
id CONICETDig_bd209cc4beef24700b02ec71b9288c37
oai_identifier_str oai:ri.conicet.gov.ar:11336/4625
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathwayGargini, RicardoCerliani, Juan PabloEscoll, MaribelAnton, Ines M.Wandosell, FranciscoStem CellsAktFoxoBimhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Many solid tumors contain a subpopulation of cells with stem characteristics and these are known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). These cells drive tumor growth and appear to be regulated by molecular pathway different from other cells in the tumor bulk. Here, we set out to determine whether elements of the PI3K-AKT pathway are necessary to maintain the CSC-like phenotype in breast tumor cells and for these cells to survive, bearing in mind that the identification of such elements is likely to be relevant to define future therapeutic targets. Our results demonstrate a close relationship between the maintenance of the CSC-like phenotype and the survival of these TICs. Inhibiting PI3K activity, or eliminating AKT activity, mostly that of the AKT1 isoform, produces a clear drop in TICs survival, and a reduction in the generation and growth of CD44(High) /CD24(Low) mammospheres. Surprisingly, the apoptosis of these TICs that is triggered by AKT1 deficiency is also associated with a loss of the stem cell/mesenchymal phenotype and a recovery of epithelial-like markers. Finally, we define downstream effectors that are responsible for controlling the CSC-phenotype, such as FoxO-Bim, and the death of these cells in the absence of AKT1. In summary, these data closely link the maintenance of the stem cell-like phenotype and the survival of these cells to the AKT-FoxO-Bim pathway.Fil: Gargini, Ricardo. Universidad Autonoma de Madrid. Centro de Biologia Molecular; EspañaFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Escoll, Maribel. Universidad Autonoma de Madrid. Centro de Biologia Molecular; España. Consejo Superior de Investigaciones Cientificas. Centro Nacional de Biotecnologia; EspañaFil: Anton, Ines M.. Consejo Superior de Investigaciones Cientificas. Centro Nacional de Biotecnologia; España. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas; EspañaFil: Wandosell, Francisco. Universidad Autonoma de Madrid. Centro de Biologia Molecular; EspañaWiley2015-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/4625Gargini, Ricardo; Cerliani, Juan Pablo; Escoll, Maribel; Anton, Ines M.; Wandosell, Francisco; Cancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathway; Wiley; Stem Cells; 33; 3; 3-2015; 646-6601066-50991549-4918enginfo:eu-repo/semantics/altIdentifier/ark/http://onlinelibrary.wiley.com/doi/10.1002/stem.1904/abstractinfo:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/doi:10.1002/stem.1904info:eu-repo/semantics/altIdentifier/issn/1066-5099info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:21:57Zoai:ri.conicet.gov.ar:11336/4625instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:21:58.019CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathway
title Cancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathway
spellingShingle Cancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathway
Gargini, Ricardo
Stem Cells
Akt
Foxo
Bim
title_short Cancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathway
title_full Cancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathway
title_fullStr Cancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathway
title_full_unstemmed Cancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathway
title_sort Cancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathway
dc.creator.none.fl_str_mv Gargini, Ricardo
Cerliani, Juan Pablo
Escoll, Maribel
Anton, Ines M.
Wandosell, Francisco
author Gargini, Ricardo
author_facet Gargini, Ricardo
Cerliani, Juan Pablo
Escoll, Maribel
Anton, Ines M.
Wandosell, Francisco
author_role author
author2 Cerliani, Juan Pablo
Escoll, Maribel
Anton, Ines M.
Wandosell, Francisco
author2_role author
author
author
author
dc.subject.none.fl_str_mv Stem Cells
Akt
Foxo
Bim
topic Stem Cells
Akt
Foxo
Bim
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Many solid tumors contain a subpopulation of cells with stem characteristics and these are known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). These cells drive tumor growth and appear to be regulated by molecular pathway different from other cells in the tumor bulk. Here, we set out to determine whether elements of the PI3K-AKT pathway are necessary to maintain the CSC-like phenotype in breast tumor cells and for these cells to survive, bearing in mind that the identification of such elements is likely to be relevant to define future therapeutic targets. Our results demonstrate a close relationship between the maintenance of the CSC-like phenotype and the survival of these TICs. Inhibiting PI3K activity, or eliminating AKT activity, mostly that of the AKT1 isoform, produces a clear drop in TICs survival, and a reduction in the generation and growth of CD44(High) /CD24(Low) mammospheres. Surprisingly, the apoptosis of these TICs that is triggered by AKT1 deficiency is also associated with a loss of the stem cell/mesenchymal phenotype and a recovery of epithelial-like markers. Finally, we define downstream effectors that are responsible for controlling the CSC-phenotype, such as FoxO-Bim, and the death of these cells in the absence of AKT1. In summary, these data closely link the maintenance of the stem cell-like phenotype and the survival of these cells to the AKT-FoxO-Bim pathway.
Fil: Gargini, Ricardo. Universidad Autonoma de Madrid. Centro de Biologia Molecular; España
Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Escoll, Maribel. Universidad Autonoma de Madrid. Centro de Biologia Molecular; España. Consejo Superior de Investigaciones Cientificas. Centro Nacional de Biotecnologia; España
Fil: Anton, Ines M.. Consejo Superior de Investigaciones Cientificas. Centro Nacional de Biotecnologia; España. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas; España
Fil: Wandosell, Francisco. Universidad Autonoma de Madrid. Centro de Biologia Molecular; España
description Many solid tumors contain a subpopulation of cells with stem characteristics and these are known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). These cells drive tumor growth and appear to be regulated by molecular pathway different from other cells in the tumor bulk. Here, we set out to determine whether elements of the PI3K-AKT pathway are necessary to maintain the CSC-like phenotype in breast tumor cells and for these cells to survive, bearing in mind that the identification of such elements is likely to be relevant to define future therapeutic targets. Our results demonstrate a close relationship between the maintenance of the CSC-like phenotype and the survival of these TICs. Inhibiting PI3K activity, or eliminating AKT activity, mostly that of the AKT1 isoform, produces a clear drop in TICs survival, and a reduction in the generation and growth of CD44(High) /CD24(Low) mammospheres. Surprisingly, the apoptosis of these TICs that is triggered by AKT1 deficiency is also associated with a loss of the stem cell/mesenchymal phenotype and a recovery of epithelial-like markers. Finally, we define downstream effectors that are responsible for controlling the CSC-phenotype, such as FoxO-Bim, and the death of these cells in the absence of AKT1. In summary, these data closely link the maintenance of the stem cell-like phenotype and the survival of these cells to the AKT-FoxO-Bim pathway.
publishDate 2015
dc.date.none.fl_str_mv 2015-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/4625
Gargini, Ricardo; Cerliani, Juan Pablo; Escoll, Maribel; Anton, Ines M.; Wandosell, Francisco; Cancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathway; Wiley; Stem Cells; 33; 3; 3-2015; 646-660
1066-5099
1549-4918
url http://hdl.handle.net/11336/4625
identifier_str_mv Gargini, Ricardo; Cerliani, Juan Pablo; Escoll, Maribel; Anton, Ines M.; Wandosell, Francisco; Cancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathway; Wiley; Stem Cells; 33; 3; 3-2015; 646-660
1066-5099
1549-4918
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/ark/http://onlinelibrary.wiley.com/doi/10.1002/stem.1904/abstract
info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/doi:10.1002/stem.1904
info:eu-repo/semantics/altIdentifier/issn/1066-5099
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846082612713488384
score 13.22299

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