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One main antioxidant enzyme is mitochondrial superoxide dismutase (SOD2) which has been shown to influence tumor initiation and metastatic progression in several cancer types.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To investigate the impact of\n                      <jats:italic>Sod2<\/jats:italic>\n                      deletion on pancreatic cancer biology and metabolism, we used CRISPR\/Cas9 gene editing to generate 3 independent\n                      <jats:italic>Sod2-<\/jats:italic>\n                      deficient cell lines from murine Kras\n                      <jats:sup>G12D<\/jats:sup>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Proliferation and wound healing capacity were significantly impaired in\n                      <jats:italic>Sod2<\/jats:italic>\n                      deficient cell lines. Myc levels were significantly elevated in\n                      <jats:italic>Sod2<\/jats:italic>\n                      -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\n                      <jats:italic>Sod2<\/jats:italic>\n                      -deficient cells. This resulted in increased peroxynitrite formation which was the cause of increased Myc activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings reveal that\n                      <jats:italic>Sod2<\/jats:italic>\n                      shapes cellular metabolism in pancreatic cancer through peroxynitrite formation and Myc activation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-025-02555-8","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T12:53:22Z","timestamp":1765025602000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mitochondrial superoxide dismutase controls metabolic plasticity in pancreatic cancer"],"prefix":"10.1186","volume":"23","author":[{"given":"Sankaranarayanan","family":"Ramasubramanian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupert","family":"\u00d6llinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Eberhagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Zischka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland M.","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Einw\u00e4chter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"2555_CR1","first-page":"12","volume":"74","author":"RL Siegel","year":"2024","unstructured":"Siegel RL, Giaquinto AN, Jemal A. 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