Peer-reviewed
Hydrogen peroxide-producing NADPH oxidases and the promotion of migratory phenotypes in cancer
The cellular microenvironment plays a critical role in cancer initiation and progression. Exposure to oxidative stress, specifically hydrogen peroxide (H2O2), has been linked to aberrant cellular signaling through which the development of cancer may be promoted. Three members of the NADPH oxidase family (NOX4, DUOX1 and DUOX2) explicitly generate this non-radical oxidant in a wide range of tissues, often in support of the inflammatory response. This review summarizes the contributions of each H2O2-producing NOX to the invasive behaviors of tumors and/or the epithelial-mesenchymal transition (EMT) in cancer that plays an essential role in metastasis. Tissue localization in tumorigenesis is also highlighted, with patient-derived TCGA microarray data profiled across 31 cancer cohorts to provide a comprehensive guide to the relevance of NOX4/DUOX1/DUOX2 in cancer studies.
• Intracellular hydrogen peroxide can promote oxidative stress leading to invasive cellular characteristics. • NADPH oxidase enzymes NOX4, DUOX1 and DUOX2 are prominent sources of hydrogen peroxide linked to cancer and metastasis. • Intracellular ROS production from the NOX4 enzyme is critical to promoting invadopodia formation. • Substantial DUOX1 promoter methylation evokes expression loss, impacting lung cancer cell migration and EMT status. • Hydrogen peroxide, produced by DUOX2, contributes to chemoresistance-induced EMT in colon cancer cells
• Intracellular hydrogen peroxide can promote oxidative stress leading to invasive cellular characteristics. • NADPH oxidase enzymes NOX4, DUOX1 and DUOX2 are prominent sources of hydrogen peroxide linked to cancer and metastasis. • Intracellular ROS production from the NOX4 enzyme is critical to promoting invadopodia formation. • Substantial DUOX1 promoter methylation evokes expression loss, impacting lung cancer cell migration and EMT status. • Hydrogen peroxide, produced by DUOX2, contributes to chemoresistance-induced EMT in colon cancer cells
Article, 2019