PRDX4 and Its Roles in Various Cancers

Abstract

Reactive oxygen species play a vital role in cell survival by regulating physiological metabolism and signal transduction of cells. The imbalance of oxidant and antioxidant states induces oxidative stress within a cell. Redox regulation and oxidative stress are closely related to survival and proliferation of stem cells, cancer cells, and cancer stem cells. Peroxiredoxin 4, a typical endoplasmic reticulum-resident 2-Cys antioxidant of peroxiredoxins, can fine-tune hydrogen peroxide catabolism which affects cell survival by affecting redox balance, oxidative protein folding, and regulation of hydrogen peroxide signaling. Recent studies revealed the overexpression of peroxiredoxin 4 in several kinds of cancers, such as breast cancer, prostate cancer, ovarian cancer, colorectal cancer, and lung cancer. And it has been demonstrated that peroxiredoxin 4 causally contributes to tumorigenesis, therapeutic resistance, metastasis, and recurrence of tumors. In this article, the characteristics of peroxiredoxin 4 in physiological functions and the cancer-related research progress of mammalian peroxiredoxin 4 is reviewed. We believe that peroxiredoxin 4 has the potential of serving as a novel target for multiple cancers.

Overexpression of PRDX4 Modulates Tumor Microenvironment and Promotes Urethane-Induced Lung Tumorigenesis

“…The latest study in hepatoblastoma (HB) indicated that PRDX4 promoted embryonal hepatoblastoma cell migration but induced fetal hepatoblastoma cell differentiation [ 18 ]. As different levels of reactive oxygen species (ROS), including H 2 O 2 , in tumor microenvironment exert specific effects on tumor [ 19 ], tumor microenvironment may also affect the role of PRDX4 in tumor via the crosstalk between PRDX4 and oxidative stress. In summary, PRDX4 plays different roles in different tumor contexts, including tumor histological type, tumor stage, and even tumor microenvironment, such as the oxidative stress balance.…”

R-catcher, a potent molecular tool to unveil the arginylome

“…It regulates the activation of NF-kB by modulating IkB alpha phosphorylation. Recent studies have shown that it plays a key role in cancer progression across different types of cancer [ 46 ].…”

NOX4 links metabolic regulation in pancreatic cancer to endoplasmic reticulum redox vulnerability and dependence on PRDX4

“…Another important aspect of personalized medicine is patient selection. PRDX4 is overexpressed in diseases like prostate cancer, lung cancer, colorectal cancer, breast cancer, ovarian cancer, and lymph node metastases from oral cavity squamous cell carcinoma ( 57 ) and is associated with poor outcome in early-stage lung squamous cell carcinoma ( 58 ). Here, we showed that PRDX4 expression is associated with aggressive disease and that higher expression confers poor outcome in resectable pancreatic cancer (fig.…”