Articles producció científica> Medicina i Cirurgia

Oncometabolic Nuclear Reprogramming of Cancer Stemness

  • Dades identificatives

    Identificador: PC:1460
    Autors:
    Jorge JovenJavier A. MenendezBruna Corominas-FajaElisabet CuyàsMaría G. GarcíaSalvador Fernández-ArroyoAgustín F. FernándezMario F. FragaTomás Alarcón
    Resum:
    By impairing histone demethylation and locking cells into a reprogramming-prone state, oncometabolites can partially mimic the process of induced pluripotent stem cell generation. Using a systems biology approach, combining mathematical modeling, computation, and proof-of-concept studies with live cells, we found that an oncometabolite-driven pathological version of nuclear reprogramming increases the speed and efficiency of dedifferentiating committed epithelial cells into stem-like states with only a minimal core of stemness transcription factors. Our biomathematical model, which introduces nucleosome modification and epigenetic regulation of cell differentiation genes to account for the direct effects of oncometabolites on nuclear reprogramming, demonstrates that oncometabolites markedly lower the "energy barriers" separating non-stem and stem cell attractors, diminishes the average time of nuclear reprogramming, and increases the size of the basin of attraction of the macrostate occupied by stem cells. These findings establish the concept of oncometabolic nuclear reprogramming of stemness as a bona fide metabolo-epigenetic mechanism for generation of cancer stem-like cells.
  • Altres:

    Autor segons l'article: Jorge Joven; Javier A. Menendez; Bruna Corominas-Faja; Elisabet Cuyàs; María G. García; Salvador Fernández-Arroyo; Agustín F. Fernández; Mario F. Fraga; Tomás Alarcón
    Departament: Medicina i Cirurgia
    Autor/s de la URV: JOVEN MARIED, JORGE; Javier A. Menendez; Bruna Corominas-Faja; Elisabet Cuyàs; María G. García; Salvador Fernández-Arroyo; Agustín F. Fernández; Mario F. Fraga; Tomás Alarcón
    Paraules clau: cercar cancer stem cells Oncometabolites
    Resum: By impairing histone demethylation and locking cells into a reprogramming-prone state, oncometabolites can partially mimic the process of induced pluripotent stem cell generation. Using a systems biology approach, combining mathematical modeling, computation, and proof-of-concept studies with live cells, we found that an oncometabolite-driven pathological version of nuclear reprogramming increases the speed and efficiency of dedifferentiating committed epithelial cells into stem-like states with only a minimal core of stemness transcription factors. Our biomathematical model, which introduces nucleosome modification and epigenetic regulation of cell differentiation genes to account for the direct effects of oncometabolites on nuclear reprogramming, demonstrates that oncometabolites markedly lower the "energy barriers" separating non-stem and stem cell attractors, diminishes the average time of nuclear reprogramming, and increases the size of the basin of attraction of the macrostate occupied by stem cells. These findings establish the concept of oncometabolic nuclear reprogramming of stemness as a bona fide metabolo-epigenetic mechanism for generation of cancer stem-like cells.
    Grup de recerca: Unitat de Recerca Biomèdica
    Àrees temàtiques: Ciències de la salut Ciencias de la salud Health sciences
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 2213-6711
    Identificador de l'autor: N/D; N/D; N/D; N/D; N/D; N/D; N/D; N/D; N/D
    Data d'alta del registre: 2016-04-27
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Enllaç font original: https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(15)00377-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221367111500377X%3Fshowall%3Dtrue
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    DOI de l'article: 10.1016/j.stemcr.2015.12.012
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2016
    Tipus de publicació: Article Artículo Article
  • Paraules clau:

    Cèl·lules canceroses
    cercar
    cancer stem cells
    Oncometabolites
    Ciències de la salut
    Ciencias de la salud
    Health sciences
    2213-6711
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