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

dc.creatorGargini, Ricardo
dc.creatorCerliani, Juan Pablo
dc.creatorEscoll, Maribel
dc.creatorAnton, Ines M.
dc.creatorWandosell, Francisco
dc.date2015-03
dc.identifierhttp://hdl.handle.net/11336/4625
dc.identifierGargini, 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
dc.identifier1066-5099
dc.identifier1549-4918
dc.descriptionMany 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.
dc.descriptionFil: Gargini, Ricardo. Universidad Autonoma de Madrid. Centro de Biologia Molecular; España
dc.descriptionFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
dc.descriptionFil: Escoll, Maribel. Universidad Autonoma de Madrid. Centro de Biologia Molecular; España. Consejo Superior de Investigaciones Cientificas. Centro Nacional de Biotecnologia; España
dc.descriptionFil: Anton, Ines M.. Consejo Superior de Investigaciones Cientificas. Centro Nacional de Biotecnologia; España. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas; España
dc.descriptionFil: Wandosell, Francisco. Universidad Autonoma de Madrid. Centro de Biologia Molecular; España
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherWiley
dc.relationinfo:eu-repo/semantics/altIdentifier/ark/http://onlinelibrary.wiley.com/doi/10.1002/stem.1904/abstract
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/doi:10.1002/stem.1904
dc.relationinfo:eu-repo/semantics/altIdentifier/issn/1066-5099
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subjectStem Cells
dc.subjectAkt
dc.subjectFoxo
dc.subjectBim
dc.subjecthttps://purl.org/becyt/ford/1.6
dc.subjecthttps://purl.org/becyt/ford/1
dc.subjecthttps://purl.org/becyt/ford/3.1
dc.subjecthttps://purl.org/becyt/ford/3
dc.titleCancer stem cell-like phenotype and survival are coordinately regulated by Akt/FoxO/Bim pathway
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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