論文 - 詳細
| RRC ID | 76686 |
|---|---|
| 著者 | Peng S, Wang Z, Tang P, Wang S, Huang Y, Xie Q, Wang Y, Tan X, Tang T, Yan X, Xu J, Lan W, Wang L, Zhang D, Wang B, Pan T, Qin J, Jiang J, Liu Q. |
| タイトル | PHF8-GLUL axis in lipid deposition and tumor growth of clear cell renal cell carcinoma. |
| ジャーナル | Sci Adv |
| Abstract |
For clear cell renal cell carcinoma (ccRCC), lipid deposition plays important roles in the development, metastasis, and drug resistance. However, the molecular mechanisms underlying lipid deposition in ccRCC remain largely unknown. By conducting an unbiased CRISPR-Cas9 screening, we identified the epigenetic regulator plant homeodomain finger protein 8 (PHF8) as an important regulator in ccRCC lipid deposition. Moreover, PHF8 is regulated by von Hippel-Lindau (VHL)/hypoxia-inducible factor (HIF) axis and essential for VHL deficiency-induced lipid deposition. PHF8 transcriptionally up-regulates glutamate-ammonia ligase (GLUL), which promotes the lipid deposition and ccRCC progression. Mechanistically, by forming a complex with c-MYC, PHF8 up-regulates TEA domain transcription factor 1 (TEAD1) in a histone demethylation-dependent manner. Subsequently, TEAD1 up-regulates GLUL transcriptionally. Pharmacological inhibition of GLUL by l-methionine sulfoximine not only repressed ccRCC lipid deposition and tumor growth but also enhanced the anticancer effects of everolimus. Thus, the PHF8-GLUL axis represents a potential therapeutic target for ccRCC treatment. |
| 巻・号 | 9(31) |
| ページ | eadf3566 |
| 公開日 | 2023-8-2 |
| DOI | 10.1126/sciadv.adf3566 |
| PMID | 37531433 |
| PMC | PMC10396305 |
| MeSH | Carcinoma, Renal Cell* / metabolism Cell Line, Tumor Gene Expression Regulation, Neoplastic Glutamate-Ammonia Ligase* / metabolism Histone Demethylases* / metabolism Humans Kidney Neoplasms* / metabolism Lipids Protein Processing, Post-Translational Transcription Factors* / genetics Transcription Factors* / metabolism |
| IF | 13.117 |
| 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 | 3 |
| 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 | |
| ヒト・動物細胞 | OS-RC-2(RCB0735) |