Autor según el artículo: Jorge Joven; Javier A. Menendez; Bruna Corominas-Faja; Elisabet Cuyàs; María G. García; Salvador Fernández-Arroyo; Agustín F. Fernández; Mario F. Fraga; Tomás Alarcón
Departamento: Medicina i Cirurgia
Autor/es 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
Palabras clave: cercar cancer stem cells Oncometabolites
Resumen: 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.
Grupo de investigación: Unitat de Recerca Biomèdica
Áreas temáticas: Ciències de la salut Ciencias de la salud Health sciences
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 2213-6711
Identificador del autor: N/D; N/D; N/D; N/D; N/D; N/D; N/D; N/D; N/D
Fecha de alta del registro: 2016-04-27
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
Enlace a la fuente 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
DOI del artículo: 10.1016/j.stemcr.2015.12.012
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2016
Tipo de publicación: Article Artículo Article
Repositori URV