The homeoprotein SIX1 controls cellular senescence through the regulation of p16INK4A and differentiation-related genes.

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 organo

SUBMITTER: Adrados I 

PROVIDER: S-EPMC5730042 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature