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Simple Summary: Reactive oxygen species (ROS) are unstable derivatives of oxygen that are generated naturally as products or biproducts of biological reactions. ROS, such as hydrogen peroxide, can be utilized for defense against infectious agents and as messengers in the biological system. However, excess ROS can damage DNA, lipids, and proteins, possibly inactivating or altering their functions. The molecules utilized by the body to stop production of ROS, to neutralize excess ROS, or to repair damage caused by ROS are known as antioxidants. Peroxiredoxins (Prxs) are one of the antioxidant enzymes expressed in species from bacteria to humans that protect cells against ROS. In recent years, great progress has been made in understanding the role of Prxs in normal physiology and in different diseases. In this review, we have briefly summarized the recent findings regarding Prxs in cancer. 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 H2O2, Prxs are among the first defenses against oxidative stress. Prxs undergo reversible oxidation to disulfides, and some family members perform chaperone or phospholipase functions upon further oxidation. Prxs are upregulated in cancer cells. Research has suggested that Prxs can function as tumor promoters in various cancers. The major objective of this review is to summarize novel findings regarding the roles of Prxs in common cancer types. Prxs have been shown to influence differentiation of inflammatory cells and fibroblasts, remodeling of extracellular matrix, and regulation of stemness. Since aggressive cancer cells have higher intracellular levels of ROS that they can utilize to proliferate and metastasize compared to normal cells, it is critical that we understand the regulation and functions of primary antioxidants such as Prxs. These small but mighty proteins could prove to be key for improving cancer therapeutics and patient survival. [ABSTRACT FROM AUTHOR]

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. Fascin, an actin-bundling protein, was discovered and validated as one of the critical downstream targets of Srx activation. We demonstrated that depletion of Srx in CRC cells leads to upregulation of miR143-3p, which mediates degradation of fascin mRNA through binding to conserved sites within the 3′ untranslated region (UTR). Depletion of fascin in CRC cells recapitulates the effect of Srx loss, and restoration of fascin in Srx-depleted cells by miR143-3p inhibitor or overexpression rescues defects in cell invasion. Therefore, our data demonstrate that the Srx-miR143-fascin axis plays a key role in promoting the malignancy of human CRC cells. In the future, the Srx-miR143-fascin axis can be used as a functional pathway to evaluate the efficacy of therapeutic drugs or be targeted to develop promising chemotherapeutics for treatment of CRC patients. [ABSTRACT FROM AUTHOR]