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