| First Author | He C | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 47 | Pages | 23534-23541 |
| PubMed ID | 31591207 | Mgi Jnum | J:282331 |
| Mgi Id | MGI:6380562 | Doi | 10.1073/pnas.1902308116 |
| Citation | He C, et al. (2019) SOD2 acetylation on lysine 68 promotes stem cell reprogramming in breast cancer. Proc Natl Acad Sci U S A 116(47):23534-23541 |
| abstractText | 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 2alpha (HIF2alpha), a transcription factor upstream of "stemness" genes such as Oct4, Sox2, and Nanog. In this sense, our findings indicate that SOD2(K68Ac) and mtROS are linked to stemness reprogramming in breast cancer cells via HIF2alpha signaling. Based on these findings we propose that, as tumors evolve, the accumulation of SOD2(K68Ac) turns on a mitochondrial pathway to stemness that depends on HIF2alpha and may be relevant for the progression of breast cancer toward poor outcomes. |
