title: SOD1, an unexpected novel target for cancer therapy.
abstract: Cancer cells have elevated levels of reactive oxygen species (ROS), which are generated in majority by the mitochondria. In the mitochondrial matrix, the manganese dismutase SOD2 acts as a major anti-oxidant enzyme. The deacetylase SIRT3 regulates the activity of SOD2. Recently, SIRT3 was reported to be decreased in 87% of breast cancers, resulting therefore in a decrease in the activity of SOD2 and an elevation in ROS. In addition to SIRT3, we recently reported that SOD2 itself is down-regulated in breast cancer cell lines upon activation of oncogenes, such as Ras. Since in absence of SOD2, superoxide levels are elevated and may cause irreversible damage, mechanisms must exist to retain superoxide below a critical threshold and maintain viability of cancer cells. The copper/zinc dismutase SOD1 localizes in the cytoplasm, the inter-membrane space of the mitochondria and the nucleus. Emerging evidences from several groups now indicate that SOD1 is overexpressed in cancers and that the activity of SOD1 may be essential to maintain cellular ROS under this critical threshold. This review summarizes the studies reporting important roles of SOD1 in cancer and addresses the potential cross-talk between the overexpression of SOD1 and the regulation of the mitochondrial unfolded protein response (UPR(mt)). While mutations in SOD1 is the cause of 20% of cases of familial amyotrophic lateral sclerosis (fALS), a devastating neurodegenerative disease, these new studies expand the role of SOD1 to cancer.
authors: From the Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY.
authors: Luena
authors: L
authors: Papa
authors: The Weill Cornell Medical College, Department of Neurology and Neuroscience, New York, New York.
authors: Giovanni
authors: G
authors: Manfredi
authors: From the Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY.
authors: Doris
authors: D
authors: Germain
keywords: SIRT3; SOD1; SOD2; cancer; fALS