SOD2 acetylation on lysine 68 promotes stem cell reprogramming in breast cancer.
Acetylation
Animals
Basic Helix-Loop-Helix Transcription Factors
/ physiology
Breast Neoplasms
/ metabolism
Cell Self Renewal
/ physiology
Cellular Reprogramming
Disease Progression
Female
Heterografts
Humans
Hydrogen Peroxide
/ metabolism
MCF-7 Cells
Mice
Mice, Inbred NOD
Mice, SCID
Mitochondria
/ enzymology
Neoplasm Invasiveness
Neoplasm Proteins
/ chemistry
Neoplastic Stem Cells
/ physiology
Protein Processing, Post-Translational
Recombinant Proteins
/ metabolism
Superoxide Dismutase
/ chemistry
MnSOD
SOD2
acetylation
breast cancer
stem cells
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
19 11 2019
19 11 2019
Historique:
pubmed:
9
10
2019
medline:
21
4
2020
entrez:
9
10
2019
Statut:
ppublish
Résumé
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 SOD2
Identifiants
pubmed: 31591207
pii: 1902308116
doi: 10.1073/pnas.1902308116
pmc: PMC6876149
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
Neoplasm Proteins
0
Recombinant Proteins
0
endothelial PAS domain-containing protein 1
1B37H0967P
Hydrogen Peroxide
BBX060AN9V
Superoxide Dismutase
EC 1.15.1.1
superoxide dismutase 2
EC 1.15.1.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
23534-23541Subventions
Organisme : NCI NIH HHS
ID : R01 CA200669
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK052913
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL125356
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA152799
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI131267
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA152601
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA216882
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES028149
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA214025
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA253678
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA168292
Pays : United States
Commentaires et corrections
Type : CommentIn
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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