SIX1 represses senescence and promotes SOX2-mediated cellular plasticity during tumorigenesis.

ABSTRACT: Six1 is a developmental transcriptional regulator frequently overexpressed in human tumors. Recent results show that SIX1 also acts as a repressor of cell senescence, an antiproliferative response with a key role in tumor suppression, among other physiological and pathological settings. Here, we set to study the impact of SIX1 gain of function in transformation and tumorigenesis of fibroblasts, in connection with senescence. Using transcriptomic, histological, and functional analyses in murine tumors and cells of fibroblast origin, we show that SIX1 has a strong pro-tumorigenic action in this model, linked to the repression of a senescence-related gene signature and the induction of an undifferentiated phenotype mediated, at least in part, by the regulation of the stemness factor Sox2. Mor

SUBMITTER: De Lope C 

PROVIDER: S-EPMC6363751 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature