Hydrogen peroxide-producing NADPH oxidases and the promotion of migratory phenotypes in cancer

Arch Biochem Biophys. 2019 Oct 30:675:108076. doi: 10.1016/j.abb.2019.108076. Epub 2019 Aug 12.

Abstract

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.

Keywords: Dual oxidase; EMT; Hydrogen peroxide; Metastasis; NOX4.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Carcinogenesis
  • Dual Oxidases / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Silencing
  • Humans
  • Hydrogen Peroxide / metabolism*
  • NADPH Oxidases / biosynthesis*
  • Neoplasm Metastasis*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Oxidative Stress
  • Phenotype
  • Tumor Microenvironment

Substances

  • Hydrogen Peroxide
  • Dual Oxidases
  • NADPH Oxidases
  • DUOX2 protein, human