SOD2 acetylation on lysine 68 promotes stem cell reprogramming in breast cancer.

ABSTRACT: Mitochondrial superoxide dismutase (SOD2) suppresses tumor initiation but promotes invasion and dissemination of tumor cells at later stages of the disease. The mechanism of this functional switch remains poorly defined. Our results indicate that as SOD2 expression increases acetylation of lysine 68 ensues. Acetylated SOD2 promotes hypoxic signaling via increased mitochondrial reactive oxygen species (mtROS). mtROS, in turn, stabilize hypoxia-induced factor 2? (HIF2?), a transcription factor upstream of "stemness" genes such as Oct4, Sox2, and Nanog. In this sense, our findings indicate that SOD2K68Ac and mtROS are linked to stemness reprogramming in breast cancer cells via HIF2? signaling. Based on these findings we propose that, as tumors evolve, the accumulation of SOD2K68Ac turns on a mitochondrial pathway to stemness that depends on HIF2? and may be relevant for the progression of breast cancer toward poor outcomes.

SUBMITTER: He C 

PROVIDER: S-EPMC6876149 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature