Forshaw Tom E, Holmila Reetta, Nelson Kimberly J, Lewis Joshua E, Kemp Melissa L, Tsang Allen W, Poole Leslie B, Lowther W Todd, Furdui Cristina M
Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Antioxidants (Basel). 2019 Jan 1;8(1):11. doi: 10.3390/antiox8010011.
Peroxiredoxins have a long-established cellular function as regulators of redox metabolism by catalyzing the reduction of peroxides (e.g., H₂O₂, 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.
过氧化物酶通过高效催化过氧化物（如过氧化氢、脂质过氧化物）的还原，作为氧化还原代谢的调节剂，在细胞中具有长期确立的功能。在广泛的病理生理背景下，这种活性对于磷酸化和氧化还原信号的启动和传递也至关重要。在正常生理条件下，过氧化物酶保护正常细胞免受可能促进肿瘤发生的氧化损伤（如环境应激源）。在癌症中，过氧化物酶的高表达水平与肿瘤生长和对放射治疗的抗性均有关联。然而，从癌症基因组图谱（TCGA）或NCI60癌细胞系面板的数据分析中，过氧化物酶表达与对辐射的反应之间的这种关系并不明显。本综述的重点是总结目前将这类蛋白质与癌症相关联的实验知识，并就靶向过氧化物酶在癌症治疗中的价值提供一个观点。还强调了在分析TCGA数据时关于辐射抗性的潜在偏差。
