Gamma-Glutamylcyclotransferase: A Novel Target Molecule for Cancer Diagnosis and Treatment

Abstract

Gamma-glutamylcyclotransferase (GGCT) is one of the major enzymes involved in glutathione metabolism. However, its gene locus was unknown for many years. Recently, the gene for GGCT was found to be identical to C7orf24, which is registered as a hypothetical protein. Orthologs have been found in bacteria, plants, and nematodes as well as higher organisms, and the GGCT gene is highly preserved among a wide range of species. GGCT (C7orf24) was also reported as an upregulated protein in various cancers. Although the function of GGCT in cancer cells has not been determined, the following important activities have been reported: (1) high expression in various cancer tissues and cancer cell lines, (2) low expression in normal tissues, (3) inhibition of cancer cell proliferation via anti-GGCT RNAi, (4) inhibition of cancer cell invasion and migration via anti-GGCT RNAi, (5) an epigenetic transcriptional regulation in cancer cells, and (6) an antitumor effect in cancer-bearing xenograft mice. Therefore, GGCT is promising as a diagnostic marker and a therapeutic target for various cancers. This review summarizes these interesting findings.

iTRAQ‐Based Quantitative Proteomics Approach Identifies Novel Diagnostic Biomarkers That Were Essential for Glutamine Metabolism and Redox Homeostasis for Gastric Cancer

“…Adequate amounts of glutamate, cysteine, and glycine are essential to maintain glutathione at proper levels. Glutathione is a tripeptide consisting of glutamates, cysteines, and glycines, which serve as a crucial antioxidative and detoxifying molecular in cells …”

Depletion of γ-glutamylcyclotransferase inhibits breast cancer cell growth via cellular senescence induction mediated by CDK inhibitor upregulation

“…A growing body of evidence indicates that GGCT is a promising candidate as a therapeutic target and biomarker in cancer [ 7 ]. To date, however, the mechanisms underlying the inhibition of cancer cell growth induced by GGCT knockdown remain unknown.…”

“…Regional injection [ 5 ] and systemic administration [ 6 ] of GGCT siRNA exerted anti-tumor effects in xenograft models in vivo. These findings suggest that GGCT is a promising candidate as a therapeutic target and diagnostic marker [ 7 ]. However, the cellular events associated with GGCT depletion have not been fully characterized to date, and the mechanisms underlying its inhibitory effect on the growth of cancer cells remain unknown.…”

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

“…γ-Glutamylcyclotransferase (GGCT, 188 amino acids, 21 kDa) is an enzyme involved in glutathione metabolism [ 1 ], and has recently been described to be overexpressed in a variety of cancers (breast, ovarian, cervical, lung, urinary bladder, colon cancers, osteosarcoma, esophageal squamous cell carcinoma, and glioma) and as a critical player in cancer cell proliferation [ 2 ]. Indeed, depletion of GGCT inhibits the aggressive phenotype of various cancers.…”