The Role of Peroxiredoxins in Cancer Development.

Peroxiredoxins (Prxs) are antioxidant enzymes with ubiquitous expression in human tissues. Prxs are expressed in archaea, bacteria, and eukaryota, often in multiple isoforms. Because of their abundant expression in different cellular organelles and extraordinary sensitivity to HO, Prxs are among the first defenses against oxidative stress.

Loss of Peroxiredoxin IV Protects Mice from Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development.

Peroxiredoxin IV (Prx4), a typical two-cysteine-containing member of the peroxidase family, functions as an antioxidant to maintain cellular redox homeostasis through the reduction of reactive oxygen species (ROS) via cycles of oxidation-reduction reactions. Under oxidative stress, all Prxs including Prx4 are inactivated as their catalytic cysteines undergo hyperoxidation, and hyperoxidized two-cysteine Prxs can be exclusively repaired and revitalized through the reduction cycle catalyzed by sulfiredoxin (Srx). Previously, we showed that Prx4 is a preferred substrate of Srx, and knockout of Srx in mice leads to resistance to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis.

Critical Role of the Sulfiredoxin-Peroxiredoxin IV Axis in Urethane-Induced Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC), the most common type of lung cancer, etiologically associates with tobacco smoking which mechanistically contributes to oxidative stress to facilitate the occurrence of mutations, oncogenic transformation and aberrantly activated signaling pathways. Our previous reports suggested an essential role of Sulfiredoxin (Srx) in promoting the development of lung cancer in humans, and was causally related to Peroxiredoxin IV (Prx4), the major downstream substrate and mediator of Srx-enhanced signaling. To further explore the role of the Srx-Prx4 axis in de novo lung tumorigenesis, we established Prx4 and Srx/Prx4 mice in pure FVB/N background.

Essential Roles of Peroxiredoxin IV in Inflammation and Cancer.

Peroxiredoxin IV (Prx4) is a 2-Cysteine peroxidase with ubiquitous expression in human tissues. Prx4 scavenges hydrogen peroxide and participates in oxidative protein folding in the endoplasmic reticulum. In addition, Prx4 is secreted outside the cell.

Protein Disulfide Isomerases Function as the Missing Link Between Diabetes and Cancer.

Diabetes has long been recognized as an independent risk factor for cancer, but there is insufficient mechanistic understanding of biological mediators that bridge two disorders together. Understanding the pathogenic association between diabetes and cancer has become the focus of many studies, and findings are potentially valuable for the development of effective preventive or therapeutic strategies for both disorders. A summary of literature reveals a possible connection between diabetes and cancer through the family of protein disulfide isomerase (PDI).

Peroxiredoxin IV plays a critical role in cancer cell growth and radioresistance through the activation of the Akt/GSK3 signaling pathways.

High levels of redox enzymes have been commonly observed in various types of human cancer, although whether and how the enzymes contribute to cancer malignancy and therapeutic resistance have yet to be understood. Peroxiredoxin IV (Prx4) is an antioxidant with bona fide peroxidase and molecular chaperone functions. Here, we report that Prx4 is highly expressed in prostate cancer patient specimens, as well as established prostate cancer cell lines, and that its levels can be further stimulated through the activation of androgen receptor signaling.

Sulfiredoxin Promotes Cancer Cell Invasion through Regulation of the miR143-Fascin Axis.

Intracellular antioxidant enzymes are critical for maintenance of redox homeostasis, but whether and how they contribute to the malignancy of cancer cells remains poorly understood. Sulfiredoxin (Srx) is a unique oxidoreductase in that it not only restores peroxidase activity of peroxiredoxins (Prxs) but also functions as a pivotal stimulator of oncogenic signaling. We found that abnormally high level of Srx promotes colorectal cancer (CRC) malignancy by stimulating gelatin degradation, invadopodia formation, and cell invasion.

The redox regulator sulfiredoxin forms a complex with thioredoxin domain-containing 5 protein in response to ER stress in lung cancer cells.

Sulfiredoxin (Srx) reduces hyperoxidized 2-cysteine-containing peroxiredoxins (Prxs) and protects cells against oxidative stress. Previous studies have shown that Srx is highly expressed in primary specimens of lung cancer patients and plays a pivotal role in lung tumorigenesis and cancer progression. However, the oncogenic mechanisms of Srx in cancer are incompletely understood.