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

Abstract	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.
Authors	Jorge de la Rosa, José M P Freije, Rubén Cabanillas, Fernando G Osorio, Mario F Fraga, M Soledad Fernández-García, Roland Rad, Víctor Fanjul, Alejandro P Ugalde, Qi Liang, Haydn M Prosser, Allan Bradley, Juan Cadiñanos, Carlos López-Otín
Journal	Nature communications (Nat Commun) Vol. 4 Pg. 2268 ( 2013) ISSN: 2041-1723 [Electronic] England
PMID	23917225 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Biomarkers Lamin Type A Membrane Proteins Nuclear Proteins Protein Precursors prelamin A Metalloendopeptidases Zmpste24 protein, mouse
Topics	Aging (pathology) Animals Biomarkers (metabolism) Carcinogenesis (pathology) Female Humans Lamin Type A Male Membrane Proteins (deficiency, metabolism) Metalloendopeptidases (deficiency, metabolism) Mice Mosaicism Neoplasm Invasiveness Neoplasms (metabolism, pathology) Nuclear Proteins (metabolism) Phenotype Progeria (metabolism, pathology) Protein Precursors (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!