論文

査読有り 国際誌
2020年4月

Epigenetic remodelling shapes inflammatory renal cancer and neutrophil-dependent metastasis

Nature Cell Biology
  • Jun Nishida
  • ,
  • Yusaku Momoi
  • ,
  • Kosuke Miyakuni
  • ,
  • Yusuke Tamura
  • ,
  • Kei Takahashi
  • ,
  • Daizo Koinuma
  • ,
  • Kohei Miyazono
  • ,
  • Shogo Ehata

22
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

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
DOI
https://doi.org/10.1038/s41556-020-0491-2
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32203421
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85083041161&origin=inward
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85083041161&origin=inward
ID情報
  • DOI : 10.1038/s41556-020-0491-2
  • ISSN : 1465-7392
  • eISSN : 1476-4679
  • PubMed ID : 32203421
  • SCOPUS ID : 85083041161

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