Autor según el artículo: Jorge Joven; Javier A. Menendez; Núria Folguera-Blasco; Elisabet Cuyàs; Salvador Fernández-Arroyo; Tomás Alarcón
Departamento: Medicina i Cirurgia
Autor/es de la URV: JOVEN MARIED, JORGE; Javier A. Menendez; Núria Folguera-Blasco; Elisabet Cuyàs; Salvador Fernández-Arroyo; Tomás Alarcón
Palabras clave: Gerotarget Geroncogenesis Cancer
Resumen: The geroncogenesis hypothesis postulates that the decline in metabolic cellular health that occurs naturally with aging drives a "field effect" predisposing normal tissues for cancer development. We propose that mutations in the cancer susceptibility genes BRCA1/2 might trigger "accelerated geroncogenesis" in breast and ovarian epithelia. By speeding up the rate at which the metabolic threshold becomes "permissive" with survival and expansion of genomically unstable pre-tumoral epithelial cells, BRCA haploinsufficiency-driven metabolic reprogramming would operate as a bona fide oncogenic event enabling malignant transformation and tumor formation in BRCA carriers. The metabolic facet of BRCA1 one-hit might involve tissue-specific alterations in acetyl-CoA, a-ketoglutarate, NAD+, FAD, or S-adenosylmethionine, critical factors for de/methylation or de/acetylation dynamics in the nuclear epigenome. This in turn might induce faulty epigenetic reprogramming at the "install phase" that directs cell-specific differentiation of breast/ovarian epithelial cells, which can ultimately determine the penetrance of BRCA defects during developmental windows of susceptibility. This model offers a framework to study whether metabolic drugs that prevent or revert metabolic reprogramming induced by BRCA haploinsufficiency might displace the "geroncogenic risk" of BRCA carriers to the age typical for those without the mutation. The identification of the key nodes that directly communicate changes in cellular metabolism to the chromatin in BRCA haploinsufficient cells may allow the epigenetic targeting of genomic instability using exclusively metabolic means. The validation of accelerated geroncogenesis as an inherited "one-hit" metabolic "field effect" might offer new strategies to therapeutically revisit the apparently irreversible genetic-hereditary fate of women with hereditary breast-ovarian cancer syndrome.
Grupo de investigación: Unitat de Recerca Biomèdica
Áreas temáticas: Health sciences Ciencias de la salud Ciències de la salut
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 1949-2553
Identificador del autor: N/D; N/D; N/D; N/D; N/D; N/D
Fecha de alta del registro: 2016-04-29
Página final: 11971
Volumen de revista: 7
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
Enlace a la fuente original: https://www.oncotarget.com/article/7867/text/
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
DOI del artículo: 10.18632/oncotarget.7867
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2016
Página inicial: 11959
Tipo de publicación: Article Artículo Article
Repositori URV