title: Gamma-glutamylcyclotransferase promotes the growth of human glioma cells by activating Notch-Akt signaling.
abstract: Glioma as an aggressive type tumor is rapidly growing and has become one of the leading cause of cancer-related death worldwide. γ-Glutamylcyclotransferase (GGCT) has been shown as a diagnostic marker in various cancers. To reveal whether there is a correlation between GGCT and human glioma, GGCT expression in human glioma tissues and cell lines was first determined. We found that GGCT expression was up-regulated in human glioma tissues and cell lines. Further, we demonstrate that GGCT knockdown inhibits glioma cell T98G and U251 proliferation and colony formation, whereas GGCT overexpression leads to oppose effects. GGCT overexpression promotes the expression of Notch receptors and activates Akt signaling in glioma cells, and Notch-Akt signaling is activated in glioma tissues with high expression of GGCT. Finally, we show that inhibition of Notch-Akt signaling with Notch inhibitor MK-0752 blocks the effects of GGCT on glioma proliferation and colony formation. In conclusion, GGCT plays a critical role in glioma cell proliferation and may be a potential cancer therapeutic target.
authors.affiliation: Medical College of Xiamen University, Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, China.
authors.forename: Shang-Hang
authors.initials: SH
authors.lastname: Shen
authors.affiliation: Medical College of Xiamen University, Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yu
authors.affiliation: Medical College of Xiamen University, Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, China.
authors.forename: Xi-Yao
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Medical College of Xiamen University, Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, China.
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Tan
authors.affiliation: Medical College of Xiamen University, Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, China. Electronic address: md_wzx7189@163.com.
authors.forename: Zhan-Xiang
authors.initials: ZX
authors.lastname: Wang
mesh_terms: D001555:Benzene Derivatives / Q000494:pharmacology; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D011422:Propionates / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013450:Sulfones / Q000494:pharmacology; D005722:gamma-Glutamylcyclotransferase / Q000235:genetics / Q000378:metabolism*
chemical_list: C554093:3-(4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acid; D001555:Benzene Derivatives; C572776:GGCT protein, human; D011422:Propionates; D051880:Receptors, Notch; D013450:Sulfones; D051057:Proto-Oncogene Proteins c-akt; D005722:gamma-Glutamylcyclotransferase
keywords: Akt; GGCT; Glioma; Notch