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Ramasubramanian, S.* ; Öllinger, R.* ; Eberhagen, C. ; Zischka, H. ; Schmid, R.M.* ; Einwächter, H.*

Mitochondrial superoxide dismutase controls metabolic plasticity in pancreatic cancer.

Cell Commun. Signal. 23:524 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: The role of reactive oxygen species (ROS) in cancer is debated. One main antioxidant enzyme is mitochondrial superoxide dismutase (SOD2) which has been shown to influence tumor initiation and metastatic progression in several cancer types. METHODS: To investigate the impact of Sod2 deletion on pancreatic cancer biology and metabolism, we used CRISPR/Cas9 gene editing to generate 3 independent Sod2-deficient cell lines from murine KrasG12D pancreatic cancer cell lines and analyzed them for proliferation, colony forming, mitochondrial respiration and RNA expression. In addition, mass spectrometry and isotope tracing were performed. RESULTS: Proliferation and wound healing capacity were significantly impaired in Sod2 deficient cell lines. Myc levels were significantly elevated in Sod2-deficient cells, and mitochondrial respiration was consecutively increased. This resulted in increased tolerance to glucose deprivation. Mechanistically, we detected a significantly reduced activity of succinate dehydrogenase (SDH) in Sod2-deficient cells. This resulted in increased peroxynitrite formation which was the cause of increased Myc activation. CONCLUSIONS: These findings reveal that Sod2 shapes cellular metabolism in pancreatic cancer through peroxynitrite formation and Myc activation.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Myc Proto-oncogene Proteins ; Pancreatic Neoplasms ; Superoxide Dismutase (sod2); Respiratory-chain; Oxidative Stress; Complex Ii; In-vitro; Myc; Growth; Cells; Apoptosis; Release
ISSN (print) / ISBN 1478-811X
e-ISSN 1478-811X
Journal Cell Communication and Signaling
Quellenangaben Volume: 23, Issue: 1, Pages: , Article Number: 524 Supplement: ,
Publisher Bmc
Publishing Place Campus, 4 Crinan St, London N1 9xw, England
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOX)
Grants Technische Universitt Mnchen (1025)