Mitochondrial antioxidant enzyme (SOD2) at the crossroads of redox signaling and cancer progression

Normal cells preferably utilize mitochondrial oxidative phosphorylation as the primary source of energy in aerobic conditions. However, superoxide anions (<b>^.</b>O₂<b>^-</b>) are produced as a by-product due to leakage of the electron from the electron transport chain during oxidative phosphorylation, and cells are continuously exposed to elevated levels of superoxide. Superoxide dismutase 2 (SOD2, also called manganese superoxide dismutase or MnSOD) is a mitochondria-matrix-localized antioxidant enzyme that prevents oxidative damage to mitochondria by converting <b>^.</b>O₂<b>^-</b> to hydrogen peroxide (H₂O₂). Previous studies reported the roles of SOD2 in regulating cellular metabolism and the connection of variable SOD2 levels and activity with diverse types and stages of cancer. In this review, we systematically summarize recent findings on the roles of SOD2 in cancer cell proliferation, cell cycle progression, invasion, metastasis, metabolic reprogramming, apoptosis, autophagy, angiogenesis, and immune response. Understanding the regulatory factors and signaling pathways of cancer development and progression mediated by SOD2 could help to target critical cellular vulnerabilities to develop novel therapeutic strategies against cancer.