Peroxiredoxins in Cancer and Response to Radiation Therapies

• 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
• Journal Title: Antioxidants
• Volume: Volume 8, Number 1
• Publisher: MDPI | 2019-01-01
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3390/antiox8010011
• Subjects: Chemistry, Biochemistry; Biology, Molecular; Health Sciences, Pharmacology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; Chemistry, Medicinal; Food Science & Technology; Pharmacology & Pharmacy; peroxiredoxin; radiation resistance; ionizing radiation; oxidative stress; transcriptomics; proteomics; TCGA; NCI-60; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; MITOCHONDRIAL COMPLEX-III; S-TRANSFERASE-PI; REACTIVE OXYGEN; OXIDATIVE STRESS; 2-CYS PEROXIREDOXIN; IONIZING-RADIATION; HYDROGEN-PEROXIDE; PROSTATE-CANCER; ANTIOXIDANT ENZYME

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.