title: Manganese Superoxide Dismutase Acetylation and Dysregulation, Due to Loss of SIRT3 Activity, Promote a Luminal B-Like Breast Carcinogenic-Permissive Phenotype.
abstract: Breast cancer is the most common nondermatologic malignancy among women in the United States, among which endocrine receptor-positive breast cancer accounts for up to 80%. Endocrine receptor-positive breast cancers can be categorized molecularly into luminal A and B subtypes, of which the latter is an aggressive form that is less responsive to endocrine therapy with inferior prognosis.
  
  
  
  Sirtuin, an aging-related gene involved in mitochondrial metabolism, is associated with life span, and more importantly, murine models lacking Sirt3 spontaneously develop tumors that resemble human luminal B breast cancer. Furthermore, these tumors exhibit aberrant manganese superoxide dismutase (MnSOD) acetylation at lysine 68 and lysine 122 and have abnormally high reactive oxygen species (ROS) levels, which have been observed in many types of breast cancer.
  
  
  
  The mechanism of how luminal B breast cancer develops resistance to endocrine therapy remains unclear. MnSOD, a primary mitochondrial detoxification enzyme, functions by scavenging excessive ROS from the mitochondria and maintaining mitochondrial and cellular homeostasis. Sirt3, a mitochondrial fidelity protein, can regulate the activity of MnSOD through deacetylation. In this study, we discuss a possible mechanism of how loss of SIRT3-guided MnSOD acetylation results in endocrine therapy resistance of human luminal B breast cancer.
  
  
  
  Acetylation of MnSOD and other mitochondrial proteins, due to loss of SIRT3, may explain the connection between ROS and development of luminal B breast cancer and how luminal B breast cancer becomes resistant to endocrine therapy. Antioxid. Redox Signal. 25, 326-336.
authors.affiliation: 1 Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University , Chicago, Illinois.|2 Department of Pharmacology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University , Chicago, Illinois.|3 Driskill Graduate Program in Life Science, Feinburg School of Medicine, Northwestern University , Chicago, Illinois.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Zou
authors.affiliation: 4 Division of Medical Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University , Chicago, Illinois.
authors.forename: Cesar Augusto
authors.initials: CA
authors.lastname: Santa-Maria
authors.affiliation: 1 Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University , Chicago, Illinois.|2 Department of Pharmacology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University , Chicago, Illinois.
authors.forename: Joseph
authors.initials: J
authors.lastname: O'Brien
authors.affiliation: 1 Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University , Chicago, Illinois.|2 Department of Pharmacology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University , Chicago, Illinois.
authors.forename: David
authors.initials: D
authors.lastname: Gius
authors.affiliation: 1 Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University , Chicago, Illinois.|2 Department of Pharmacology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University , Chicago, Illinois.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000107:Acetylation; D000375:Aging / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D004789:Enzyme Activation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015994:Incidence; D008136:Longevity / Q000235:genetics; D008239:Lysine / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D010641:Phenotype; D012008:Recurrence; D056566:Sirtuin 3 / Q000235:genetics* / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D013482:Superoxide Dismutase; D056566:Sirtuin 3; D008239:Lysine