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

Kageyama, Susumu; Hiromi,; Taniguchi, Keiko; Kubota, Shigehisa; Yoshida, Tetsuya; Isono, Takahiro; Chano, Tokuhiro; Yoshiya, Taku; Ito, Kosei; Tokura, Y.; Kawauchi, Akihiro; Nakata, Susumu

doi:10.3390/ijms19072054

Cited by 41 publications

(29 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The disruption of GGCT in HCT-116 cells markedly decreased the EMT associated markers and changed the morphology of GGCT-knockdown HCT-116 cells from mesenchymal-like cell type to the epithelial cell type, compared with the control cells. Disrupting GGCT was also observed to notably decrease the cell migration and invasion of HCT-116 cells, which was consistent with previous reports that indicated that GGCT influenced the migration and invasion of cancer cells ( 5 , 31 ).…”

Section: Discussionsupporting

confidence: 92%

GGCT promotes colorectal cancer migration and invasion via epithelial‑mesenchymal transition

Huang

Zhou

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the most common malignancies, and the fourth most common cause of cancer-associated mortality globally. The epithelial to mesenchymal transition (EMT) serves an important function in metastatic dissemination and determines the aggressiveness of CRC. However, the regulatory mechanism of EMT in CRC has not yet been elucidated. γ-glutamylcyclotransferase (GGCT) is an important enzyme in glutathione metabolism and highly expressed in numerous forms of cancer, making it a promising therapeutic target. In the present study, GGCT was demonstrated to be highly expressed in CRC tissues, and patients with CRC with a higher expression of GGCT exhibited a worse prognosis compared with patients exhibiting a lower expression of GGCT. This result suggests that GGCT may serve as a novel prognostic marker for CRC. Furthermore, GGCT was indicated to promote CRC cell migration and invasion through regulating EMT-associated genes, including N-cadherin, Vimentin, snail family transcriptional repressor 2 and snail family transcriptional repressor 1. In conclusion, the present study provides novel insights into the mechanism governing CRC migration and invasion, and identified GGCT as a promising therapeutic target that may be used in the treatment of CRC.

show abstract

Section: Discussionsupporting

confidence: 92%

GGCT promotes colorectal cancer migration and invasion via epithelial‑mesenchymal transition

Huang

Zhou

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…GSH is a tripeptide consisting of glutamate, cysteine, and glycine, and its biosynthesis cycle requires γ-glutamylcyclotransferase, 5-oxoprolinase, glutamate cysteine ligase, and glutathione synthase [ 22 ]. Because mitochondrial GSH has a central role in ROS regulation, the depletion of GSH may be relevant to the development of steatohepatitis and NASH [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Regulation of hepatic genes related to lipid metabolism and antioxidant enzymes by sodium butyrate supplementation

et al. 2020

View full text Add to dashboard Cite

Background Rapid influx of energy caused by fasting/refeeding repeatedly enhances fatty acid synthesis leading to triacylglycerol accumulation and production of reactive oxygen species (ROS), increasing the risk of non-alcoholic steatohepatitis (NASH). Previous studies have reported that the ingestion of butyrate is effective at preventing hepatic disorders, which are accompanied by fat accumulation and inflammation. The aim of this study is to reveal the mechanism of action of butyrate, and thus we investigated the effects of dietary butyrate on the expressions of antioxidant enzymes in the livers of rats during refeeding following fasting. Methods Thirty-seven male rats were divided into six groups (6–7 animals per group): non-fasting, fasting, refeeding with a high sucrose diet as control for 12 or 24 h, and refeeding with a high sucrose diet containing 5% sodium butyrate (NaB) for 12 or 24 h. All groups except the non-fasting group were fasted for 72 h before refeeding. Statistical analysis was conducted among 4 refeeding groups (refeeding with the control diet for 12 or 24 h, and refeeding with a diet containing NaB for 12 or 24 h). Results Supplementation with NaB significantly reduced ( p < 0.05) fatty acid synthase ( Fas ) gene expression and increased the expression of the carnitine palmitoyltransferase 1α ( Cpt1a ) gene, resulting in reduced triacylglycerol content in the livers of rats refed the NaB diet compared with controls at 24 h after the start of refeeding. The mRNA levels of the genes related to glutathione synthesis were significantly higher ( p < 0.05) in the livers of the butyrate group than the control group. In addition, the mRNA level of Foxo3a , a transcription factor that regulates the expressions of antioxidant enzymes, was higher in the butyrate group than controls. The acetylation levels of histone H4 around the Foxo3a gene tended to be increased ( p = 0.055) by refeeding with the NaB diet. Conclusion NaB supplementation in the diet for refeeding reduced the rate of lipid synthesis and stimulated fatty acid oxidation in the liver, which inhibited fat accumulation and the risk of NASH. The transcriptional regulation of Foxo3a involves histone acetylation around the gene.

show abstract

“…PFKFB1 can be used as a potential molecular target for thyroid biotherapy. The GGCT play a role in cell proliferation, and the expression of this gene is a potential marker for cancer [57] .…”

Section: Discussionmentioning

confidence: 99%

Excavating thyroid carcinoma risk metabolic genes associated with biological clock by bioinformatics analysis: A study based on TCGA and GEO data

wang

Zhang

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Thyroid carcinoma (TC) is malignant tumor of the endocrine gland with a significantly increased incidence in recent years, which related to metabolic diseases and biological clock disorder. The molecular mechanism and risk metabolic genes associated with biological clock of TC require conducting study. Methods We mined differentially expressed genes of TC (TC-DEGs) from TCGA and GEO database. Searching for biorhythm related genes (BRGs) based on core clock genes by STRING analysis. Next, we used a series of bioinformatics methods to analyze the TC-DEGs and BRGs, including chromosome location, GO and KEGG pathway annotation. Then, we extracted the expression of statistically significant TC metabolic genes by Perl program combined with a computational method of GSEA. Furthermore, screen the risk metabolic genes and reveal potential underlying KEGG pathways of the gene signatures. Results Our results identified 474 DEGs (P < 0.05; |log FC| > 1) in patients with TC compared with the normal controls using the available numerical mRNA expression values. The chromosomal assignments of TC-DEGs and BRGs were inhomogeneous. These genes were mainly distributed on Chrom01, 02, 11, 12, 04, 03 and X, none of the associated genes were distributed on sex Y chromosome. ARNTL and BHLHE40 belong to both the TC-DEGs and BRGs. PER2, NCOR1, RXRG, CCND1, SERPINE1 and PLAU were mined which act as the hub of signaling pathways linking “Thyroid hormone signaling pathway”, “Circadian rhythm”, “Transcriptional misregulation in cancer” and so on. One hundred and forty-one metabolic genes were extracted to train the prognostic model, and 11 risk genes were found, among them, 10 risk gene products have indirect interaction with ARNTL and BHLHE40. Such important genes for TC were regulated by many common conserved microRNAs. Conclusions Our study identified 8 key genes and 11 risk metabolic genes of thyroid carcinoma associated with biological clock by bioinformatics analysis. And the coding products of these genes form a clear interaction network, which is conducive to further study the molecular mechanism, reveal the role of circadian clock genes and metabolic genes in thyroid cancer.

show abstract

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

Cited by 41 publications

References 31 publications

GGCT promotes colorectal cancer migration and invasion via epithelial‑mesenchymal transition

GGCT promotes colorectal cancer migration and invasion via epithelial‑mesenchymal transition

Regulation of hepatic genes related to lipid metabolism and antioxidant enzymes by sodium butyrate supplementation

Excavating thyroid carcinoma risk metabolic genes associated with biological clock by bioinformatics analysis: A study based on TCGA and GEO data

Contact Info

Product

Resources

About