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

• DOI: 10.1038/ncomms3268
• Publication Date: 2013-08-06T10:06:04Z
• Authors: Jorge de la Rosa; José M.P. Freije; Rubén Cabanillas; Fernando G. Osorio; Mario F. Fraga; M. Soledad Fernán...; Roland Rad; Víctor Fanjul; Alejandro P. Ugalde; Qi Liang; Haydn M. Prosser; Allan Bradley; Juan Cadiñanos; Carlos López-Otín
• Keywords: Progeria; Nuclear lamina

Abstract Defining the relationship between ageing and cancer is a crucial but challenging task. Mice deficient in Zmpste24, metalloproteinase mutated human progeria involved nuclear prelamin A maturation, recapitulate multiple features of ageing. However, their short lifespan serious cell-intrinsic cell-extrinsic alterations restrict application interpretation carcinogenesis protocols. Here we present Zmpste24 mosaic mice that lack these limitations. develop normally keep similar proportions Zmpste24-deficient (prelamin A-accumulating) Zmpste24-proficient (mature lamin A-containing) cells throughout life, revealing mechanisms are preeminent for development. Moreover, accumulation does not impair tumour initiation growth, it decreases incidence infiltrating oral carcinomas. Accordingly, silencing ZMPSTE24 reduces cell invasiveness. Our results support potential cell-based systemic therapies highlight as new anticancer target.