論文 - 詳細
| RRC ID | 67865 |
|---|---|
| 著者 | Takayama KI, Kosaka T, Suzuki T, Hongo H, Oya M, Fujimura T, Suzuki Y, Inoue S. |
| タイトル | Subtype-specific collaborative transcription factor networks are promoted by OCT4 in the progression of prostate cancer. |
| ジャーナル | Nat Commun |
| Abstract |
Interactive networks of transcription factors (TFs) have critical roles in epigenetic and gene regulation for cancer progression. It is required to clarify underlying mechanisms for transcriptional activation through concerted efforts of TFs. Here, we show the essential role of disease phase-specific TF collaboration changes in advanced prostate cancer (PC). Investigation of the transcriptome in castration-resistant PC (CRPC) revealed OCT4 as a key TF in the disease pathology. OCT4 confers epigenetic changes by promoting complex formation with FOXA1 and androgen receptor (AR), the central signals for the progression to CRPC. Meanwhile, OCT4 facilitates a distinctive complex formation with nuclear respiratory factor 1 (NRF1) to gain chemo-resistance in the absence of AR. Mechanistically, we reveal that OCT4 increases large droplet formations with AR/FOXA1 as well as NRF1 in vitro. Disruption of TF collaborations using a nucleoside analogue, ribavirin, inhibited treatment-resistant PC tumor growth. Thus, our findings highlight the formation of TF collaborations as a potent therapeutic target in advanced cancer. |
| 巻・号 | 12(1) |
| ページ | 3766 |
| 公開日 | 2021-6-18 |
| DOI | 10.1038/s41467-021-23974-4 |
| PII | 10.1038/s41467-021-23974-4 |
| PMID | 34145268 |
| PMC | PMC8213733 |
| MeSH | Animals Antineoplastic Agents / pharmacology Cell Line, Tumor Cell Proliferation / genetics Disease Models, Animal Drug Resistance, Neoplasm / genetics Gene Expression Regulation / genetics Gene Expression Regulation, Neoplastic / genetics HEK293 Cells Hepatocyte Nuclear Factor 3-alpha / metabolism* Humans Male Mice Mice, Inbred BALB C Mice, Nude Nuclear Respiratory Factor 1 / metabolism Octamer Transcription Factor-3 / genetics* Octamer Transcription Factor-3 / metabolism* Prostatic Neoplasms, Castration-Resistant / genetics* Prostatic Neoplasms, Castration-Resistant / pathology Receptors, Androgen / metabolism* Ribavirin / pharmacology Signal Transduction Transcriptome / genetics |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 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 | Venus/pCS2 (RDB15116) |