Mechanisms of Tumor Growth Inhibition by Depletion of γ-Glutamylcyclotransferase (GGCT): A Novel Molecular Target for Anticancer Therapy

Int J Mol Sci. 2018 Jul 14;19(7):2054. doi: 10.3390/ijms19072054.

Abstract

γ-Glutamylcyclotransferase (GGCT), which is one of the major enzymes involved in glutathione metabolism, is upregulated in a wide range of cancers-glioma, breast, lung, esophageal, gastric, colorectal, urinary bladder, prostate, cervical, ovarian cancers and osteosarcoma-and promotes cancer progression; its depletion leads to the suppression of proliferation, invasion, and migration of cancer cells. It has been demonstrated that the suppression or inhibition of GGCT has an antitumor effect in cancer-bearing xenograft mice. Based on these observations, GGCT is now recognized as a promising therapeutic target in various cancers. This review summarizes recent advances on the mechanisms of the antitumor activity of GGCT inhibition.

Keywords: C7orf24; GGCT; autophagy; cancer; cellular senescence.

Publication types

  • Review

MeSH terms

  • Alanine / analogs & derivatives
  • Alanine / therapeutic use*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / therapeutic use*
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics
  • Molecular Targeted Therapy / methods*
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • RNA Interference
  • gamma-Glutamylcyclotransferase / antagonists & inhibitors*
  • gamma-Glutamylcyclotransferase / genetics
  • gamma-Glutamylcyclotransferase / metabolism

Substances

  • Enzyme Inhibitors
  • MIRN194 microRNA, human
  • MicroRNAs
  • gamma-Glutamylcyclotransferase
  • Alanine