Gamma-Glutamylcyclotransferase: A Novel Target Molecule for Cancer Diagnosis and Treatment.
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.
Department of Urology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
Susumu
S
Kageyama
Department of Urology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
Eiki
E
Hanada
Department of Clinical Oncology, Kyoto Pharmaceutical University, Misasagi-Nakauchicho 5, Yamashinaku, Kyoto 607-8414, Japan.
Hiromi
H
Ii
Department of Urology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
Keiji
K
Tomita
Department of Urology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan ; Department of Clinical Oncology, Kyoto Pharmaceutical University, Misasagi-Nakauchicho 5, Yamashinaku, Kyoto 607-8414, Japan.
Tatsuhiro
T
Yoshiki
Department of Urology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
Akihiro
A
Kawauchi
D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D005722:gamma-Glutamylcyclotransferase / Q000096:biosynthesis / Q000235:genetics*
D014408:Biomarkers, Tumor; C572776:GGCT protein, human; D005722:gamma-Glutamylcyclotransferase; D005978:Glutathione