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
Article's DOI: 10.1016/j.stemcr.2015.12.012
Entity: Universitat Rovira i Virgili
Journal publication year: 2016
Publication Type: Article Artículo Article
Repositori URV