THE ROLE OF MITOCHONDRIAL ANTIOXIDANT ENZYME SUPEROXIDE DISMUTASE 2 (SOD2) IN PLURIPOTENCY AND DIFFERENTIATION

Abstract

The mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD2) is important for maintaining mitochondrial integrity and keeping the levels of reactive oxygen species (ROS) low. Small populations of poorly-differentiated cells with stem-like properties, termed cancer stem-like cells (CSLCs), have been identified in tumor masses and play an important role in chemoresistance and cancer recurrence. The purpose of this study was to examine the role of SOD2 in CSLCs. Using several models of CSLCs including: embryonal CSLCs, breast CSLCs (BCSLCs), and patient-derived brain tumor-initiating cells (BTICs), it was found that silencing of SOD2 inhibits the expression of stemness-maintaining pluripotency factors. Furthermore, the comparison of CSLCs with their non-stem like counterparts revealed that CSLCs harbor drastically higher levels of SOD2. Further mechanistic analysis demonstrated that SOD2 depletion promotes apoptosis and induces differentiation in CSLCs. In conclusion, CSLCs appear to rely on SOD2 expression for maintaining their stem-like features.