Web of Science: 21 citations, Scopus: 22 citations, Google Scholar: citations,
Oncometabolic nuclear reprogramming of cancer stemness
Menendez, Javier A. (Institut Català d'Oncologia)
Corominas-Faja, Bruna (Institut d'Investigació Biomèdica de Girona)
Cuyàs, Elisabet (Institut d'Investigació Biomèdica de Girona)
García, María G. (Instituto Universitario de Oncología del Principado de Asturias)
Fernández-Arroyo, Salvador (Hospital Universitari de Sant Joan)
Fernández, Agustín F. (Instituto Universitario de Oncología del Principado de Asturias)
Joven, Jorge (Hospital Universitari de Sant Joan)
Fraga, Mario F. (Instituto Universitario de Oncología del Principado de Asturias)
Alarcón Cor, Tomás (Centre de Recerca Matemàtica)

Date: 2016
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. Using a systems biology approach combining mathematical and computational modeling with proof-of-concept experiments in cultured cells, Menendez and colleagues provide evidence that oncometabolic versions of nuclear reprogramming phenomena are capable of generating cancer stem-like states from more differentiated counterparts. These findings offer an innovative stochastic modeling tool as well as a conceptual framework for investigating the underexplored link between cellular metabolism and cancer-initiating alterations of the epigenome at the stem cell level.
Note: Número d'acord de subvenció MICINN/SAF2012-3891
Note: Número d'acord de subvenció MICINN/MTM2011-29342
Note: Número d'acord de subvenció AGAUR/2014/SGR-1307
Note: Número d'acord de subvenció AGAUR/2014/SGR-229
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. Creative Commons
Language: Anglès
Document: article ; recerca ; publishedVersion
Subject: Oncometabolites ; Reprogramming ; Stemness ; Cancer ; Stem cells ; Cancer stem cells
Published in: Stem cell reports, Vol. 6, issue 3 (March 2016) , p. 273-283, ISSN 2213-6711

DOI: 10.1016/j.stemcr.2015.12.012
PMID: 26876667


11 p, 2.4 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles

 Record created 2018-02-07, last modified 2021-03-05



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