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

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...

Full description

Saved in:

Bibliographic Details
Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 47; pp. 23534 - 23541
Main Authors:	He, Chenxia, Danes, Jeanne M., Hart, Peter C., Zhu, Yueming, Huang, Yunping, deAbreu, Andre Luelsdorf, O’Brien, Joseph, Mathison, Angela J., Tang, Binwu, Frasor, Jonna M., Wakefield, Lalage M., Ganini, Douglas, Stauder, Erich, Zielonka, Jacek, Gantner, Benjamin N., Urrutia, Raul A., Gius, David, Bonini, Marcelo G.
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 19-11-2019
Series:	From the Cover
Subjects:	Acetylation Animals Basic Helix-Loop-Helix Transcription Factors - physiology Biological Sciences Breast cancer Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell Self Renewal - physiology Cellular Reprogramming Disease Progression Female Heterografts Humans Hydrogen Peroxide - metabolism Hypoxia Lysine MCF-7 Cells Mice Mice, Inbred NOD Mice, SCID Mitochondria Mitochondria - enzymology Neoplasm Invasiveness Neoplasm Proteins - chemistry Neoplasm Proteins - physiology Neoplastic Stem Cells - physiology Oct-4 protein PNAS Plus Protein Processing, Post-Translational Reactive oxygen species Recombinant Proteins - metabolism Signaling Stem cells Superoxide dismutase Superoxide Dismutase - chemistry Superoxide Dismutase - physiology Tumor cells Tumors acetylation stem cells breast cancer SOD2 MnSOD
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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 andmay be relevant for the progression of breast cancer toward poor outcomes.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: C.H., P.C.H., A.J.M., D. Ganini, J.Z., B.N.G., R.A.U., D. Gius, and M.G.B. designed research; C.H., J.M.D., P.C.H., Y.Z., Y.H., A.L.d.A., J.O., A.J.M., D. Ganini, E.S., J.Z., and M.G.B. performed research; Y.Z., B.T., J.M.F., L.M.W., and D. Gius contributed new reagents/analytic tools; C.H., J.M.D., P.C.H., Y.Z., A.L.d.A., A.J.M., D. Ganini, E.S., J.Z., R.A.U., D. Gius, and M.G.B. analyzed data; C.H., B.N.G., and M.G.B. wrote the paper; and L.M.W. shared protocols. Edited by Rafael Radi, Universidad de la República, Montevideo, Uruguay, and approved September 11, 2019 (received for review March 15, 2019)
ISSN:	0027-8424 1091-6490 1091-6490
DOI:	10.1073/pnas.1902308116