Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/28495
Title: The homeoprotein SIX1 controls cellular senescence through the regulation of p16INK4A and differentiation-related genes.
Authors: 
Mesh: 
Issue Date: 2016
Citation: Oncogene.2016 07;(35)27:3485-94
Abstract: Cellular senescence is an antiproliferative response with essential functions in tumor suppression and tissue homeostasis. Here we show that SIX1, a member of the SIX family of homeobox transcriptional factors, is a novel repressor of senescence. Our data show that SIX1 is specifically downregulated in fibroblasts upon oncogenic stress and other pro-senescence stimuli, as well as in senescent skin premalignant lesions. Silencing of SIX1 in human fibroblasts suffices to trigger senescence, which is mediated by p16INK4A and lacks a canonical senescence-associated secretory phenotype. Interestingly, SIX1-associated senescence is further characterized by the expression of a set of development and differentiation-related genes that significantly overlap with genes associated with SIX1 in organogenesis or human tumors, and show coincident regulation in oncogene-induced senescence. Mechanistically, we show that gene regulation by SIX1 during senescence is mediated, at least in part, by cooperation with Polycomb repressive complexes. In summary, our results identify SIX1, a key development regulator altered in human tumors, as a critical repressor of cellular senescence, providing a novel connection between senescence, differentiation and tumorigenesis.
PMID: 26500063
URI: https://hdl.handle.net/20.500.12530/28495
Rights: openAccess
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. U. La Paz > Artículos

Files in This Item:
File Description SizeFormat 
PMC5730042.pdf2.01 MBAdobe PDFThumbnail
View/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.