論文 - 詳細
| RRC ID | 76621 |
|---|---|
| 著者 | Harada Y, Mizote Y, Suzuki T, Hirayama A, Ikeda S, Nishida M, Hiratsuka T, Ueda A, Imagawa Y, Maeda K, Ohkawa Y, Murai J, Freeze HH, Miyoshi E, Higashiyama S, Udono H, Dohmae N, Tahara H, Taniguchi N. |
| タイトル | Metabolic clogging of mannose triggers dNTP loss and genomic instability in human cancer cells. |
| ジャーナル | Elife |
| Abstract |
Mannose has anticancer activity that inhibits cell proliferation and enhances the efficacy of chemotherapy. How mannose exerts its anticancer activity, however, remains poorly understood. Here, using genetically engineered human cancer cells that permit the precise control of mannose metabolic flux, we demonstrate that the large influx of mannose exceeding its metabolic capacity induced metabolic remodeling, leading to the generation of slow-cycling cells with limited deoxyribonucleoside triphosphates (dNTPs). This metabolic remodeling impaired dormant origin firing required to rescue stalled forks by cisplatin, thus exacerbating replication stress. Importantly, pharmacological inhibition of de novo dNTP biosynthesis was sufficient to retard cell cycle progression, sensitize cells to cisplatin, and inhibit dormant origin firing, suggesting dNTP loss-induced genomic instability as a central mechanism for the anticancer activity of mannose. |
| 巻・号 | 12 |
| 公開日 | 2023-7-18 |
| DOI | 10.7554/eLife.83870 |
| PII | 83870 |
| PMID | 37461317 |
| PMC | PMC10353863 |
| MeSH | Cisplatin DNA Replication Genomic Instability Humans Mannose* Neoplasms* Nucleotides |
| IF | 7.08 |
| 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 | News |
| 各媒体での言及数の合計 | 61 |
| 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 | KP4(RCB1005) HeLa(RCB0007) |