Akt Signaling Leads to Stem Cell Activation and Promotes Tumor Development in Epidermis

Authors

  • Carmen Segrelles,

    1. Molecular Oncology Unit and, Department of Basic Research, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain
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  • Ramón García-Escudero,

    1. Molecular Oncology Unit and, Department of Basic Research, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain
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  • Maria I. Garín,

    1. Division of Haematopoietic Innovative Therapies, Department of Basic Research, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain
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  • Juan F. Aranda,

    1. Molecular Oncology Unit and, Department of Basic Research, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain
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  • Pilar Hernández,

    1. Molecular Oncology Unit and, Department of Basic Research, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain
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  • José M. Ariza,

    1. Molecular Oncology Unit and, Department of Basic Research, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain
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  • Mirentxu Santos,

    1. Molecular Oncology Unit and, Department of Basic Research, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain
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  • Jesús M. Paramio,

    Corresponding author
    1. Molecular Oncology Unit and, Department of Basic Research, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain
    • Correspondence: Corina Lorz, PhD, Unidad de Oncología Molecular, Edificio 70a, CIEMAT, Avenue Complutense 22, 20840 Madrid, Spain. Telephone: 34-914962521; Fax: 34-913466484; e-mail: clorz@ciemat.es; or Jesús M. Paramio, PhD, Unidad de Oncología Molecular, Edificio 70a, CIEMAT, Avenue Complutense 22, 20840 Madrid, Spain. Telephone: 34-914962521; Fax: 34-913466484; e-mail: jesusm.paramio@ciemat.es.

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  • Corina Lorz

    Corresponding author
    1. Molecular Oncology Unit and, Department of Basic Research, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain
    • Correspondence: Corina Lorz, PhD, Unidad de Oncología Molecular, Edificio 70a, CIEMAT, Avenue Complutense 22, 20840 Madrid, Spain. Telephone: 34-914962521; Fax: 34-913466484; e-mail: clorz@ciemat.es; or Jesús M. Paramio, PhD, Unidad de Oncología Molecular, Edificio 70a, CIEMAT, Avenue Complutense 22, 20840 Madrid, Spain. Telephone: 34-914962521; Fax: 34-913466484; e-mail: jesusm.paramio@ciemat.es.

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Abstract

Hair follicle stem cells (HF-SCs) alternate between periods of quiescence and proliferation, to finally differentiate into all the cell types that constitute the hair follicle. Also, they have been recently identified as cells of origin in skin cancer. HF-SCs localize in a precise region of the hair follicle, the bulge, and molecular markers for this population have been established. Thus, HF-SCs are good model to study the potential role of oncogenic activations on SC physiology. Expression of a permanently active form of Akt (myrAkt) in basal cells leads to Akt hyperactivation specifically in the CD34+Itga6H population. This activation causes bulge stem cells to exit from quiescence increasing their response to proliferative stimuli and affecting some functions such as cell migration. HF-SC identity upon Akt activation is preserved; in this sense, increased proliferation does not result in stem cell exhaustion with age suggesting that Akt activation does not affect self-renewal an important aspect for normal tissue maintenance and cancer development. Genome-wide transcriptome analysis of HF-SC isolated from myrAkt and wild-type epidermis underscores changes in metabolic pathways characteristic of cancer cells. These differences manifest during a two-step carcinogenesis protocol in which Akt activation in HF-SCs results in increased tumor development and malignant transformation. Stem Cells 2014;32:1917–1928

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