Articles producció científica> Medicina i Cirurgia

Oncometabolic Nuclear Reprogramming of Cancer Stemness

  • Identification data

    Identifier: PC:1460
    Authors:
    Jorge JovenJavier A. MenendezBruna Corominas-FajaElisabet CuyàsMaría G. GarcíaSalvador Fernández-ArroyoAgustín F. FernándezMario F. FragaTomás Alarcón
    Abstract:
    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.
  • Others:

    Author, as appears in the 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
    Department: Medicina i Cirurgia
    URV's Author/s: 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
    Keywords: cercar cancer stem cells Oncometabolites
    Abstract: 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.
    Research group: Unitat de Recerca Biomèdica
    Thematic Areas: Ciències de la salut Ciencias de la salud Health sciences
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 2213-6711
    Author identifier: N/D; N/D; N/D; N/D; N/D; N/D; N/D; N/D; N/D
    Record's date: 2016-04-27
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: 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
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Article's DOI: 10.1016/j.stemcr.2015.12.012
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2016
    Publication Type: Article Artículo Article
  • Keywords:

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