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Antioxidants
Special Issues
The Role of Peroxiredoxins in Cancer
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The Role of Peroxiredoxins in Cancer

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Antioxidant Enzyme Systems".

Deadline for manuscript submissions: closed (31 October 2018) | Viewed by 23413

Special Issue Editor

Prof. Dr. Carola Neumann

E-Mail Website
Guest Editor
Department of Pharmacology and Chemical Biology, Magee Womens Research Institute, University of Pittsburgh Cancer Institute, 204 Craft Avenue, Pittsburgh, PA 15213, USA
Interests: peroxiredoxins; control of redox signaling; redox-induced posttranslational protein modifications; breast cancer

Special Issue Information

Dear Colleagues,

It has been proposed that cancer cells are heavily dependent on their antioxidant defences for survival and growth. Peroxiredoxins are a family of abundant thiol-dependent peroxidases that break down hydrogen peroxide, and they have a central role in the maintenance and response of cells to alterations in redox homeostasis. As such, they are potential targets for disrupting tumor growth. However, genetic disruption of peroxiredoxin expression in mice leads to an increased incidence of neoplastic disease, consistent with a role for peroxiredoxins in protecting genomic integrity and suppression of tumor initiation. Peroxiredoxin expression varies among human tumors, suggesting that in some cancers the importance of strengthened antioxidant defences may be essential for cancer cell survival. Therefore, peroxiredoxin inhibitors are being developed and explored as therapeutic agents in different cancer models. 

In order to understand better the function of peroxiredoxins in cancer, it is necessary to complement peroxiredoxin knockout and expression studies with improved understanding of their biological function. Thus, goal of this special issue is to bring together current views regarding peroxiredoxins in regulating cancer associated cellular mechanisms. These include, but are not limited to, cell stress, death and damage, cellular transformation, cancer prevention and progression (invasion and metastasis), drug resistance and cancer treatment.

Thank you for your interest!

Prof. Dr. Carola Neumann
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Peroxiredoxins
  • Cancer
  • Redox signaling
  • Redox-induced posttranslational modifications
  • Redox-induced cell damage

Related Special Issues

Published Papers (5 papers)

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Review

22 pages, 1936 KiB  
Review
Signals Getting Crossed in the Entanglement of Redox and Phosphorylation Pathways: Phosphorylation of Peroxiredoxin Proteins Sparks Cell Signaling
by John J. Skoko, Shireen Attaran and Carola A. Neumann
Antioxidants 2019, 8(2), 29; https://doi.org/10.3390/antiox8020029 - 23 Jan 2019
Cited by 21 | Viewed by 5299
Abstract
Reactive oxygen and nitrogen species have cell signaling properties and are involved in a multitude of processes beyond redox homeostasis. The peroxiredoxin (Prdx) proteins are highly sensitive intracellular peroxidases that can coordinate cell signaling via direct reactive species scavenging or by acting as [...] Read more.
Reactive oxygen and nitrogen species have cell signaling properties and are involved in a multitude of processes beyond redox homeostasis. The peroxiredoxin (Prdx) proteins are highly sensitive intracellular peroxidases that can coordinate cell signaling via direct reactive species scavenging or by acting as a redox sensor that enables control of binding partner activity. Oxidation of the peroxidatic cysteine residue of Prdx proteins are the classical post-translational modification that has been recognized to modulate downstream signaling cascades, but increasing evidence supports that dynamic changes to phosphorylation of Prdx proteins is also an important determinant in redox signaling. Phosphorylation of Prdx proteins affects three-dimensional structure and function to coordinate cell proliferation, wound healing, cell fate and lipid signaling. The advent of large proteomic datasets has shown that there are many opportunities to understand further how phosphorylation of Prdx proteins fit into intracellular signaling cascades in normal or malignant cells and that more research is necessary. This review summarizes the Prdx family of proteins and details how post-translational modification by kinases and phosphatases controls intracellular signaling. Full article
(This article belongs to the Special Issue The Role of Peroxiredoxins in Cancer)
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24 pages, 1765 KiB  
Review
Peroxiredoxins in Cancer and Response to Radiation Therapies
by Tom E. Forshaw, Reetta Holmila, Kimberly J. Nelson, Joshua E. Lewis, Melissa L. Kemp, Allen W. Tsang, Leslie B. Poole, W. Todd Lowther and Cristina M. Furdui
Antioxidants 2019, 8(1), 11; https://doi.org/10.3390/antiox8010011 - 01 Jan 2019
Cited by 33 | Viewed by 5864
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue The Role of Peroxiredoxins in Cancer)
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16 pages, 2952 KiB  
Review
Piecing Together How Peroxiredoxins Maintain Genomic Stability
by James D. West, Trevor J. Roston, Joseph B. David, Kristin M. Allan and Matthew A. Loberg
Antioxidants 2018, 7(12), 177; https://doi.org/10.3390/antiox7120177 - 28 Nov 2018
Cited by 12 | Viewed by 4647
Abstract
Peroxiredoxins, a highly conserved family of thiol oxidoreductases, play a key role in oxidant detoxification by partnering with the thioredoxin system to protect against oxidative stress. In addition to their peroxidase activity, certain types of peroxiredoxins possess other biochemical activities, including assistance in [...] Read more.
Peroxiredoxins, a highly conserved family of thiol oxidoreductases, play a key role in oxidant detoxification by partnering with the thioredoxin system to protect against oxidative stress. In addition to their peroxidase activity, certain types of peroxiredoxins possess other biochemical activities, including assistance in preventing protein aggregation upon exposure to high levels of oxidants (molecular chaperone activity), and the transduction of redox signals to downstream proteins (redox switch activity). Mice lacking the peroxiredoxin Prdx1 exhibit an increased incidence of tumor formation, whereas baker’s yeast (Saccharomyces cerevisiae) lacking the orthologous peroxiredoxin Tsa1 exhibit a mutator phenotype. Collectively, these findings suggest a potential link between peroxiredoxins, control of genomic stability, and cancer etiology. Here, we examine the potential mechanisms through which Tsa1 lowers mutation rates, taking into account its diverse biochemical roles in oxidant defense, protein homeostasis, and redox signaling as well as its interplay with thioredoxin and thioredoxin substrates, including ribonucleotide reductase. More work is needed to clarify the nuanced mechanism(s) through which this highly conserved peroxidase influences genome stability, and to determine if this mechanism is similar across a range of species. Full article
(This article belongs to the Special Issue The Role of Peroxiredoxins in Cancer)
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10 pages, 940 KiB  
Review
Cancer-Associated Function of 2-Cys Peroxiredoxin Subtypes as a Survival Gatekeeper
by Sang Won Kang, Sunmi Lee and Joanna H. S. Lee
Antioxidants 2018, 7(11), 161; https://doi.org/10.3390/antiox7110161 - 11 Nov 2018
Cited by 9 | Viewed by 3810
Abstract
Cancer cells are abnormal cells that do not comply with tissue homeostasis but undergo uncontrolled proliferation. Such abnormality is driven mostly by somatic mutations on oncogenes and tumor suppressors. Cancerous mutations show intra-tumoral heterogeneity across cancer types and eventually converge into the self-activation [...] Read more.
Cancer cells are abnormal cells that do not comply with tissue homeostasis but undergo uncontrolled proliferation. Such abnormality is driven mostly by somatic mutations on oncogenes and tumor suppressors. Cancerous mutations show intra-tumoral heterogeneity across cancer types and eventually converge into the self-activation of proliferative signaling. While transient production of intracellular reactive oxygen species (ROS) is essential for cell signaling, its persistent production is cytotoxic. Thus, cancer cells require increased levels of intracellular ROS for continuous proliferation, but overexpress cellular peroxidase enzymes, such as 2-Cys peroxiredoxins, to maintain ROS homeostasis. However, suppression of 2-Cys peroxiredoxins has also been reported in some metastatic cancers. Hence, the cancer-associated functions of 2-Cys peroxiredoxins must be illuminated in the cellular context. In this review, we describe the distinctive signaling roles of 2-Cys peroxiredoxins beyond their intrinsic ROS-scavenging role in relation to cancer cell death and survival. Full article
(This article belongs to the Special Issue The Role of Peroxiredoxins in Cancer)
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11 pages, 598 KiB  
Review
Peroxiredoxins in Colorectal Cancer: Predictive Biomarkers of Radiation Response and Therapeutic Targets to Increase Radiation Sensitivity?
by Jesse Fischer, Tim W. Eglinton, Frank A. Frizelle and Mark B. Hampton
Antioxidants 2018, 7(10), 136; https://doi.org/10.3390/antiox7100136 - 05 Oct 2018
Cited by 6 | Viewed by 3126
Abstract
Colorectal cancer (CRC) is the third most common cancer in the Western world, with one-third of cases located in the rectum. Preoperative radiotherapy is the standard of care for many patients with rectal cancer but has a highly variable response rate. The ability [...] Read more.
Colorectal cancer (CRC) is the third most common cancer in the Western world, with one-third of cases located in the rectum. Preoperative radiotherapy is the standard of care for many patients with rectal cancer but has a highly variable response rate. The ability to predict response would be of great clinical utility. The response of cells to ionizing radiation is known to involve immediate damage to biomolecules and more sustained disruption of redox homeostasis leading to cell death. The peroxiredoxins are an important group of thiol-dependent antioxidants involved in protecting cells from oxidative stress and regulating signaling pathways involved in cellular responses to oxidative stress. All six human peroxiredoxins have shown increased expression in CRC and may be associated with clinicopathological features and tumor response to ionizing radiation. Peroxiredoxins can act as markers of oxidative stress in various biological systems but they have not been investigated in this capacity in CRC. As such, there is currently insufficient evidence to support the role of peroxiredoxins as clinical biomarkers, but it is an area worthy of investigation. Future research should focus on the in vivo response of rectal cancer to radiotherapy and the redox status of peroxiredoxins in rectal cancer cells, in order to predict response to radiotherapy. The peroxiredoxin system is also a potential therapeutic target for CRC. Full article
(This article belongs to the Special Issue The Role of Peroxiredoxins in Cancer)
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