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Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion

Defining the relationship between ageing and cancer is a crucial but challenging task. Mice deficient in Zmpste24, a metalloproteinase mutated in human progeria and involved in nuclear prelamin A maturation, recapitulate multiple features of ageing. However, their short lifespan and serious cell-int...

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Autores principales: de la Rosa, Jorge, Freije, José M. P., Cabanillas, Rubén, Osorio, Fernando G., Fraga, Mario F., Fernández-García, M. Soledad, Rad, Roland, Fanjul, Víctor, Ugalde, Alejandro P., Liang, Qi, Prosser, Haydn M., Bradley, Allan, Cadiñanos, Juan, López-Otín, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758871/
https://www.ncbi.nlm.nih.gov/pubmed/23917225
http://dx.doi.org/10.1038/ncomms3268
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author de la Rosa, Jorge
Freije, José M. P.
Cabanillas, Rubén
Osorio, Fernando G.
Fraga, Mario F.
Fernández-García, M. Soledad
Rad, Roland
Fanjul, Víctor
Ugalde, Alejandro P.
Liang, Qi
Prosser, Haydn M.
Bradley, Allan
Cadiñanos, Juan
López-Otín, Carlos
author_facet de la Rosa, Jorge
Freije, José M. P.
Cabanillas, Rubén
Osorio, Fernando G.
Fraga, Mario F.
Fernández-García, M. Soledad
Rad, Roland
Fanjul, Víctor
Ugalde, Alejandro P.
Liang, Qi
Prosser, Haydn M.
Bradley, Allan
Cadiñanos, Juan
López-Otín, Carlos
author_sort de la Rosa, Jorge
collection PubMed
description Defining the relationship between ageing and cancer is a crucial but challenging task. Mice deficient in Zmpste24, a metalloproteinase mutated in human progeria and involved in nuclear prelamin A maturation, recapitulate multiple features of ageing. However, their short lifespan and serious cell-intrinsic and cell-extrinsic alterations restrict the application and interpretation of carcinogenesis protocols. Here we present Zmpste24 mosaic mice that lack these limitations. Zmpste24 mosaic mice develop normally and keep similar proportions of Zmpste24-deficient (prelamin A accumulating) and Zmpste24-proficient (mature lamin A containing) cells throughout life, revealing that cell-extrinsic mechanisms are preeminent for progeria development. Moreover, prelamin A accumulation does not impair tumour initiation and growth, but it decreases the incidence of infiltrating oral carcinomas. Accordingly, silencing of ZMPSTE24 reduces human cancer cell invasiveness. Our results support the potential of cell-based and systemic therapies for progeria and highlight ZMPSTE24 as a new anticancer target.
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spelling pubmed-37588712014-02-06 Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion de la Rosa, Jorge Freije, José M. P. Cabanillas, Rubén Osorio, Fernando G. Fraga, Mario F. Fernández-García, M. Soledad Rad, Roland Fanjul, Víctor Ugalde, Alejandro P. Liang, Qi Prosser, Haydn M. Bradley, Allan Cadiñanos, Juan López-Otín, Carlos Nat Commun Article Defining the relationship between ageing and cancer is a crucial but challenging task. Mice deficient in Zmpste24, a metalloproteinase mutated in human progeria and involved in nuclear prelamin A maturation, recapitulate multiple features of ageing. However, their short lifespan and serious cell-intrinsic and cell-extrinsic alterations restrict the application and interpretation of carcinogenesis protocols. Here we present Zmpste24 mosaic mice that lack these limitations. Zmpste24 mosaic mice develop normally and keep similar proportions of Zmpste24-deficient (prelamin A accumulating) and Zmpste24-proficient (mature lamin A containing) cells throughout life, revealing that cell-extrinsic mechanisms are preeminent for progeria development. Moreover, prelamin A accumulation does not impair tumour initiation and growth, but it decreases the incidence of infiltrating oral carcinomas. Accordingly, silencing of ZMPSTE24 reduces human cancer cell invasiveness. Our results support the potential of cell-based and systemic therapies for progeria and highlight ZMPSTE24 as a new anticancer target. 2013-08-06 /pmc/articles/PMC3758871/ /pubmed/23917225 http://dx.doi.org/10.1038/ncomms3268 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
de la Rosa, Jorge
Freije, José M. P.
Cabanillas, Rubén
Osorio, Fernando G.
Fraga, Mario F.
Fernández-García, M. Soledad
Rad, Roland
Fanjul, Víctor
Ugalde, Alejandro P.
Liang, Qi
Prosser, Haydn M.
Bradley, Allan
Cadiñanos, Juan
López-Otín, Carlos
Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion
title Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion
title_full Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion
title_fullStr Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion
title_full_unstemmed Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion
title_short Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion
title_sort prelamin a causes progeria through cell-extrinsic mechanisms and prevents cancer invasion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758871/
https://www.ncbi.nlm.nih.gov/pubmed/23917225
http://dx.doi.org/10.1038/ncomms3268
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