論文 - 詳細
| RRC ID | 63531 |
|---|---|
| 著者 | Kume K, Ikeda M, Miura S, Ito K, Sato KA, Ohmori Y, Endo F, Katagiri H, Ishida K, Ito C, Iwaya T, Nishizuka SS. |
| タイトル | α-Amanitin Restrains Cancer Relapse from Drug-Tolerant Cell Subpopulations via TAF15. |
| ジャーナル | Sci Rep |
| Abstract |
Cancer relapse occurs with substantial frequency even after treatment with curative intent. Here we studied drug-tolerant colonies (DTCs), which are subpopulations of cancer cells that survive in the presence of drugs. Proteomic characterization of DTCs identified stemness- and epithelial-dominant subpopulations, but functional screening suggested that DTC formation was regulated at the transcriptional level independent from protein expression patterns. We consistently found that α-amanitin, an RNA polymerase II (RNAPII) inhibitor, effectively inhibited DTCs by suppressing TAF15 expression, which binds to RNA to modulate transcription and RNA processing. Sequential administration of α-amanitin and cisplatin extended overall survival in a cancer-relapse mouse model, namely peritonitis carcinomatosa. Therefore, post-treatment cancer relapse may occur through non-distinct subpopulations and may be effectively prevented by α-amanitin to disrupt transcriptional machinery, including TAF15. |
| 巻・号 | 6 |
| ページ | 25895 |
| 公開日 | 2016-5-16 |
| DOI | 10.1038/srep25895 |
| PII | srep25895 |
| PMID | 27181033 |
| PMC | PMC4867652 |
| MeSH | Alpha-Amanitin / administration & dosage* Alpha-Amanitin / pharmacology Animals Cell Line, Tumor Cisplatin / administration & dosage Cisplatin / therapeutic use Down-Regulation Drug Resistance / drug effects* Enzyme Inhibitors / administration & dosage* Enzyme Inhibitors / pharmacology Gene Expression Regulation, Neoplastic / drug effects HCT116 Cells HT29 Cells HeLa Cells Humans MCF-7 Cells Mice Peritoneal Neoplasms / drug therapy* Peritoneal Neoplasms / genetics Peritoneal Neoplasms / metabolism Proteomics / methods Secondary Prevention TATA-Binding Protein Associated Factors / metabolism* Transcription, Genetic / drug effects Xenograft Model Antitumor Assays |
| IF | 3.998 |
| 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 | Patent(IFI CLAIMS) |
| 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 | |
| ヒト・動物細胞 | HCT116(RCB2979) HeLa MCF7(RCB1904) MKN45(RCB1001) |