Document Type
Article
Publication Date
8-2-2023
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.
Publication Title
Science Advances
Volume
9
Issue
31
PubMed ID
37531433
Recommended Citation
Peng, Song; Wang, Ze; Tang, Peng; Wang, Shuo; Huang, Yiqiang; Xie, Qiubo; Wang, Yapeng; Tan, Xintao; Tang, Tang; Yan, Xuzhi; Xu, Jing; Lan, Weihua; Wang, Luofu; Zhang, Dianzheng; Wang, Bin; Pan, Tiejun; Qin, Jun; Jiang, Jun; and Liu, Qiuli, "PHF8-GLUL axis in lipid deposition and tumor growth of clear cell renal cell carcinoma." (2023). PCOM Scholarly Works. 2223.
https://digitalcommons.pcom.edu/scholarly_papers/2223
Comments
This article was published in Science Advances, Volume 9, Issue 31.
The published version is available at https://doi.org/10.1126/sciadv.adf3566.
Copyright © 2023 The Authors,some rights reserved. CC BY-NC 4.0.