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SOD2 acetylation on lysine 68 promotes stem cell reprogramming in breast cancer. Proc Natl Acad Sci U S A 2019 11 19;116(47):23534-23541

Date

10/09/2019

Pubmed ID

31591207

Pubmed Central ID

PMC6876149

DOI

10.1073/pnas.1902308116

Scopus ID

2-s2.0-85075260452   6 Citations

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 2α (HIF2α), 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 HIF2α 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 HIF2α and may be relevant for the progression of breast cancer toward poor outcomes.

Author List

He C, Danes JM, Hart PC, Zhu Y, Huang Y, de Abreu AL, O'Brien J, Mathison AJ, Tang B, Frasor JM, Wakefield LM, Ganini D, Stauder E, Zielonka J, Gantner BN, Urrutia RA, Gius D, Bonini MG

Authors

Benjamin N. Gantner PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Angela Mathison PhD Assistant Professor in the Surgery department at Medical College of Wisconsin
Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin
Jacek M. Zielonka PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acetylation
Animals
Basic Helix-Loop-Helix Transcription Factors
Breast Neoplasms
Cell Self Renewal
Cellular Reprogramming
Disease Progression
Female
Heterografts
Humans
Hydrogen Peroxide
MCF-7 Cells
Mice
Mice, Inbred NOD
Mice, SCID
Mitochondria
Neoplasm Invasiveness
Neoplasm Proteins
Neoplastic Stem Cells
Protein Processing, Post-Translational
Recombinant Proteins
Superoxide Dismutase
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a