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

Chenxia He, Jeanne M. Danes, Peter C. Hart, Yueming Zhu, Yunping Huang, Andre Luelsdorf de Abreu, Joseph O’Brien, Angela J. Mathison, Binwu Tang, Jonna M. Frasor, Lalage M. Wakefield, Douglas Ganini, Erich Stauder, Jacek Zielonka, Benjamin N. Gantner, Raul A. Urrutia, David Gius, Marcelo G. Bonini*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus 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.

Original languageEnglish (US)
Pages (from-to)23534-23541
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number47
DOIs
StatePublished - 2019

Keywords

  • Acetylation
  • Breast cancer
  • MnSOD
  • SOD2
  • Stem cells

ASJC Scopus subject areas

  • General

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  • Cite this

    He, C., Danes, J. M., Hart, P. C., Zhu, Y., Huang, Y., de Abreu, A. L., O’Brien, J., Mathison, A. J., Tang, B., Frasor, J. M., Wakefield, L. M., Ganini, D., Stauder, E., Zielonka, J., Gantner, B. N., Urrutia, R. A., Gius, D., & Bonini, M. G. (2019). SOD2 acetylation on lysine 68 promotes stem cell reprogramming in breast cancer. Proceedings of the National Academy of Sciences of the United States of America, 116(47), 23534-23541. https://doi.org/10.1073/pnas.1902308116