論文 - 詳細
| RRC ID | 71642 |
|---|---|
| 著者 | Taniguchi K, Kageyama S, Moyama C, Ando S, Ii H, Ashihara E, Horinaka M, Sakai T, Kubota S, Kawauchi A, Nakata S. |
| タイトル | γ-Glutamylcyclotransferase, a novel regulator of HIF-1α expression, triggers aerobic glycolysis. |
| ジャーナル | Cancer Gene Ther |
| Abstract |
Metabolic reprogramming leading to aerobic glycolysis, termed the "Warburg effect," is a critical property of cancer cells. However, the precise mechanisms underlying this phenomenon are not fully understood. A growing body of evidence indicates that γ-glutamylcyclotransferase (GGCT), an enzyme involved in glutathione homeostasis that is highly expressed in many types of cancer, represents a promising therapeutic target. In this study, we identified GGCT as a novel regulator of hypoxia-inducible factor-1α (HIF-1α), a transcription factor that plays a role in hypoxia adaptation promoting aerobic glycolysis. In multiple human cancer cell lines, depletion of GGCT downregulated HIF-1α at the mRNA and protein levels. Conversely, in NIH3T3 mouse fibroblasts, overexpression of GGCT upregulated HIF-1α under normoxia. Moreover, depletion of GGCT downregulated HIF-1α downstream target genes involved in glycolysis, whereas overexpression of GGCT upregulated those genes. Metabolomic analysis revealed that modulation of GGCT expression induced a metabolic switch from the citric acid cycle to glycolysis under normoxia. In addition, we found that GGCT regulates expression of HIF-1α protein via the AMPK-mTORC1-4E-BP1 pathway in PC3 cells. Thus GGCT regulates the expression of HIF-1α in cancer cells, causing a switch to glycolysis. |
| 巻・号 | 29(1) |
| ページ | 37-48 |
| 公開日 | 2022-1-1 |
| DOI | 10.1038/s41417-020-00287-0 |
| PII | 10.1038/s41417-020-00287-0 |
| PMID | 33402732 |
| MeSH | Animals Cell Line, Tumor Citric Acid Cycle* Glycolysis / genetics Humans Hypoxia-Inducible Factor 1, alpha Subunit / genetics Mice NIH 3T3 Cells gamma-Glutamylcyclotransferase* / genetics |
| IF | 4.534 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | A549 |