Peroxiredoxins in Cancer and Response to Radiation Therapies

• Type of Material: Article
• Authors: Tom E. Forshaw, Wake Forest School of Medicine; Reetta Holmila, Wake Forest School of Medicine; Kimberly J. Nelson, Wake Forest School of Medicine; Joshua E. Lewis, Georgia Institute of Technology; Melissa Kemp, Emory University; Allen W. Tsang, Wake Forest School of Medicine; Leslie B. Poole, Wake Forest School of Medicine; W. Todd Lowther, Wake Forest School of Medicine; Cristina M. Furdui, Wake Forest School of Medicine
• Language: English
• Date: 2019-01-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/antiox8010011
• Title of Journal or Parent Work: Antioxidants
• ISSN: 2076-3921
• Volume: 8
• Issue: 1
• Grant/Funding Information: The authors of this review article are supported by the National Cancer Institute and National Institute of Environmental Health Sciences under award numbers R33 ES025645 (C.M.F., R.H., A.W.T.), U01 CA215848 (C.M.F., M.L.K., T.E.F., A.W.T.), R01 GM119227 (L.B.P. and W.T.L.) and F30 CA224968 (J.E.L.).
• Keywords: HYDROGEN-PEROXIDE; ionizing radiation; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; Science & Technology; OXIDATIVE STRESS; MITOCHONDRIAL COMPLEX-III; Life Sciences & Biomedicine; radiation resistance; IONIZING-RADIATION; Pharmacology & Pharmacy; TCGA; ANTIOXIDANT ENZYME; proteomics; PROSTATE-CANCER; S-TRANSFERASE-PI; Biochemistry & Molecular Biology; 2-CYS PEROXIREDOXIN; Chemistry, Medicinal; REACTIVE OXYGEN; oxidative stress; Food Science & Technology; NCI-60; peroxiredoxin; transcriptomics
• Research Categories: Chemistry, Biochemistry; Health Sciences, Pharmacology; Biology, Molecular

Abstract

Peroxiredoxins have a long-established cellular function as regulators of redox metabolism by catalyzing the reduction of peroxides (e.g., H 2 O 2 , lipid peroxides) with high catalytic efficiency. This activity is also critical to the initiation and relay of both phosphorylation and redox signaling in a broad range of pathophysiological contexts. Under normal physiological conditions, peroxiredoxins protect normal cells from oxidative damage that could promote oncogenesis (e.g., environmental stressors). In cancer, higher expression level of peroxiredoxins has been associated with both tumor growth and resistance to radiation therapies. However, this relationship between the expression of peroxiredoxins and the response to radiation is not evident from an analysis of data in The Cancer Genome Atlas (TCGA) or NCI60 panel of cancer cell lines. The focus of this review is to summarize the current experimental knowledge implicating this class of proteins in cancer, and to provide a perspective on the value of targeting peroxiredoxins in the management of cancer. Potential biases in the analysis of the TCGA data with respect to radiation resistance are also highlighted.