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Updated: Jan 7, 2026

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Mitochondrial superoxide dismutase controls metabolic plasticity in pancreatic cancer

Sankaranarayanan Ramasubramanian1, Rupert Öllinger2, Carola Eberhagen3

  • 1Department of Medicine 2, School of Medicine and Health, Technical University of Munich, Ismaninger Straße 22, Munich, 81675, Germany.

Cell Communication and Signaling : CCS
|December 6, 2025
PubMed

Insights

Mitochondrial superoxide dismutase (SOD2) deficiency impairs pancreatic cancer cell growth and alters metabolism. This involves increased Myc activation via peroxynitrite formation, impacting tumor progression.

Area of Science:

  • Oncology
  • Biochemistry
  • Cell Biology

Background:

  • The role of reactive oxygen species (ROS) in cancer remains controversial.
  • Mitochondrial superoxide dismutase (SOD2), a key antioxidant enzyme, influences tumor initiation and metastasis.

Purpose of the Study:

  • To investigate the effects of Sod2 deletion on pancreatic cancer biology and metabolism.
  • To understand the underlying mechanisms of Sod2's impact on tumor progression.

Main Methods:

  • Generated Sod2-deficient murine pancreatic cancer cell lines using CRISPR/Cas9 gene editing.
  • Analyzed proliferation, colony formation, mitochondrial respiration, and RNA expression.
  • Utilized mass spectrometry and isotope tracing for metabolic analysis.

Main Results:

  • Sod2 deficiency significantly impaired cell proliferation and wound healing.
  • Elevated Myc levels and increased mitochondrial respiration were observed in Sod2-deficient cells.
  • Reduced succinate dehydrogenase (SDH) activity led to increased peroxynitrite formation and Myc activation, enhancing glucose deprivation tolerance.

Conclusions:

  • Sod2 plays a critical role in shaping pancreatic cancer cell metabolism.
  • Peroxynitrite formation and subsequent Myc activation are key mechanisms by which Sod2 influences pancreatic cancer.
  • Targeting Sod2 or related pathways may offer therapeutic strategies for pancreatic cancer.
Keywords:
Myc Proto-Oncogene ProteinsPancreatic NeoplasmsSuperoxide Dismutase (SOD2)

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