Exploring the role of glucose‑6‑phosphate dehydrogenase in cancer (Review)

Oncol Rep. 2020 Dec;44(6):2325-2336. doi: 10.3892/or.2020.7803. Epub 2020 Oct 12.

Abstract

Glucose‑6‑phosphate dehydrogenase (G6PD) is a cytoplasmic enzyme found in human erythrocytes that provides reduced NADPH for cell metabolism. Glutathione produced by the G6PD pathway can reduce the degree of harm caused by reactive oxygen species such as oxygen‑containing free radicals, peroxides and lipid peroxides. Investigation of G6PD has long focused on hemolysis, jaundice and other diseases caused by defects in its function. However, increased mRNA expression levels of G6PD are predictive of adverse clinical outcomes in cancer patients, including increased drug resistance, migration or proliferation of tumor cells. Mutations in the G6PD gene affect protein expression and activity, and alters the balance of redox states, leading to disease. However, the association between G6PD and tumors is incompletely understood. The aim of the present review was to summarize the current body of knowledge on the role of G6PD in tumor progression and the possible regulatory mechanisms involved. It is hypothesized that G6PD will prove to be of value as a target of cancer treatment in the near future.

Keywords: G6PD; pentose phosphate pathway; NADPH; cancer; drug resistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Erythrocytes / enzymology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glucose / metabolism
  • Glucosephosphate Dehydrogenase / antagonists & inhibitors
  • Glucosephosphate Dehydrogenase / genetics*
  • Glucosephosphate Dehydrogenase / metabolism
  • Glutathione / metabolism
  • Humans
  • Mice
  • Mutation
  • NADP / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Reactive Oxygen Species / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Reactive Oxygen Species
  • NADP
  • G6PD protein, human
  • Glucosephosphate Dehydrogenase
  • Glutathione
  • Glucose