論文 - 詳細
| RRC ID | 62611 |
|---|---|
| 著者 | Nishida J, Momoi Y, Miyakuni K, Tamura Y, Takahashi K, Koinuma D, Miyazono K, Ehata S. |
| タイトル | Epigenetic remodelling shapes inflammatory renal cancer and neutrophil-dependent metastasis. |
| ジャーナル | Nat Cell Biol |
| Abstract |
Advanced clear cell renal cell carcinoma (ccRCC) frequently causes systemic inflammation. Recent studies have shown that cancer cells reshape the immune landscape by secreting cytokines or chemokines. This phenotype, called cancer-cell-intrinsic inflammation, triggers a metastatic cascade. Here, we identified the functional role and regulatory mechanism of inflammation driven by advanced ccRCC cells. The inflammatory nature of advanced ccRCC was recapitulated in a preclinical model of ccRCC. Amplification of cancer-cell-intrinsic inflammation during ccRCC progression triggered neutrophil-dependent lung metastasis. Massive expression of inflammation-related genes was transcriptionally activated by epigenetic remodelling through mechanisms such as DNA demethylation and super-enhancer formation. A bromodomain and extra-terminal motif inhibitor synchronously suppressed C-X-C-type chemokines in ccRCC cells and decreased neutrophil-dependent lung metastasis. Overall, our findings provide insight into the nature of inflammatory ccRCC, which triggers metastatic cascades, and suggest a potential therapeutic strategy. |
| 巻・号 | 22(4) |
| ページ | 465-475 |
| 公開日 | 2020-4-1 |
| DOI | 10.1038/s41556-020-0491-2 |
| PII | 10.1038/s41556-020-0491-2 |
| PMID | 32203421 |
| MeSH | Animals Carcinoma, Renal Cell / genetics* Carcinoma, Renal Cell / metabolism Carcinoma, Renal Cell / mortality Carcinoma, Renal Cell / secondary Cell Line, Tumor Chemokines, CXC / genetics Chemokines, CXC / metabolism Disease Progression Epigenesis, Genetic* Gene Expression Profiling Gene Expression Regulation, Neoplastic* Humans Inflammation Kidney Neoplasms / genetics* Kidney Neoplasms / metabolism Kidney Neoplasms / mortality Kidney Neoplasms / pathology Lung Neoplasms / genetics* Lung Neoplasms / metabolism Lung Neoplasms / mortality Lung Neoplasms / secondary Lymphatic Metastasis Male Mice Mice, Nude Neoplasm Proteins / genetics* Neoplasm Proteins / metabolism Neutrophils / metabolism Neutrophils / pathology Prognosis Survival Analysis Tumor Microenvironment / genetics Xenograft Model Antitumor Assays |
| IF | 20.042 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 40 |
| 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 | CSII-EF-RfA (RDB04387) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394) |
| ヒト・動物細胞 | OS-RC-2(RCB0735) |