SOD2 is a known tumor initiation suppressor. However, late-stage solid tumors display high levels of SOD2 expression. A group of researchers spread between Chicago (IL) Milwaukee (MI) and Research Triangle Park (NC) have reported that overexpression of SOD2 causes accumulation of an acetylated form that increases mitochondrial reactive oxygen species and an increase in HIF2α activity.
HIF2α is believed to be largely responsible for treatment failure and metastatic recurrence of breast cancer. The authors found increased SOD2 and HIF2α in metastatic lesions compared with primary tumors from the same patients. Their results suggest that the accumulation of acetylated SOD2 in later stages of cancer may promote cancer stem cell formation, leading to elevated tumor aggressiveness and poorer patient outcomes.