Epigenetic remodelling shapes inflammatory renal cancer and neutrophil-dependent metastasis
Epigenetic remodelling shapes inflammatory renal cancer and neutrophil-dependent metastasis
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DOI：
10.1038/s41556-020-0491-2
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发表时间：
2020-03-23
影响因子：
21.3
通讯作者：
Ehata, Shogo
中科院分区：
文献类型：
--
作者：
Nishida, Jun;Momoi, Yusaku;Ehata, Shogo
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.Nishida et al. show that DNA demethylation and super-enhancer formation upregulates the transcription of inflammation genes, thereby promoting neutrophil-mediated lung metastasis in renal cell carcinoma.
