2020年4月
Epigenetic remodelling shapes inflammatory renal cancer and neutrophil-dependent metastasis.
Nature cell biology
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- 巻
- 22
- 号
- 4
- 開始ページ
- 465
- 終了ページ
- 475
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s41556-020-0491-2
- 出版者・発行元
- Springer Science and Business Media LLC
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.
- リンク情報
- ID情報
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- DOI : 10.1038/s41556-020-0491-2
- ISSN : 1465-7392
- eISSN : 1476-4679
- PubMed ID : 32203421