論文 - 詳細
| RRC ID | 85526 |
|---|---|
| 著者 | Seo S, Park MJ, Park MG, Gwak M, Kim Y, Jang J, Hong N, Lee BS, Kim C, Jo S, Shim HB, Kim HJ, Kim MH, Yoo SH, Yoon S, Kim S, Lee JH, Choi SH, Lee SY, Yeon GB, Park SH, Kim SH, Lee H, Lee JY, Kim DS, Lee BC, Park JW, Kim H. |
| タイトル | DHRS13 suppresses differentiation and mitophagy in glioma via retinoic acid and mitochondrial reactive oxygen species. |
| ジャーナル | Nat Commun |
| Abstract |
To elucidate the complex interplay of undifferentiated cancer cells in malignancy, we focus on the crucial mechanisms that maintain the undifferentiated state of cancer stem-like cells, which drive tumor growth and therapy resistance. Here, we identify a protein called dehydrogenase/reductase 13 (DHRS13) that is abundant in undifferentiated glioblastoma cells. DHRS13 is primarily located in the mitochondria and functions as a retinaldehyde reductase, converting all-trans-retinaldehyde to all-trans-retinol with high affinity for NADPH. Mechanistically, DHRS13 prevents glioma stem-like cells from differentiating by blocking retinoic acid signaling, thereby maintaining their undifferentiated state. Remarkably, the depletion of DHRS13 results in mitochondrial reactive oxygen species-driven mitophagy and cell death. Consequently, loss of DHRS13 leads to a significant decrease in tumor initiation and progression. These findings hold promise for the development of strategies that target undifferentiated cancer cells, potentially leading to improved treatment outcomes. |
| 巻・号 | 16(1) |
| ページ | 6996 |
| 公開日 | 2025-7-30 |
| DOI | 10.1038/s41467-025-62148-4 |
| PII | 10.1038/s41467-025-62148-4 |
| PMID | 40739132 |
| PMC | PMC12311135 |
| MeSH | Animals Brain Neoplasms* / genetics Brain Neoplasms* / metabolism Brain Neoplasms* / pathology Cell Differentiation* Cell Line, Tumor Glioblastoma / metabolism Glioblastoma / pathology Glioma* / genetics Glioma* / metabolism Glioma* / pathology Humans Mice Mitochondria* / metabolism Mitophagy* Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology Oxidoreductases* / genetics Oxidoreductases* / metabolism Reactive Oxygen Species* / metabolism Signal Transduction Tretinoin* / metabolism |
| IF | 12.121 |
| 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 | Bluesky |
| 各媒体での言及数の合計 | 7 |
| 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 | |
| 遺伝子材料 | mito-SRAI_pcDNA3 (RDB18223) |