ArticleScience advances2023
PHF8-GLUL axis in lipid deposition and tumor growth of clear cell renal cell carcinoma.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Metabolic reprogramming-mediated therapeutic resistance in renal cell carcinoma: Mechanisms and targeted intervention strategies.iScience · 2026Review
- Rescuing the Function of Missense-Mutated Tumor SuppressorbioRxiv : the preprint server for biology · 2026Article
- Identification of central regulators related to residual feed intake in Huainan chickens based on weighted gene co-expression network analysis.Poultry science · 2026Article
- Bioinformatics and clinical analysis reveal the potential diagnostic and prognostic role of DLD for pan cancer and renal carcinoma.Discover oncology · 2026Article
- GLUL Confers Perivascular Cancer-Associated Fibroblasts With Pro-Angiogenic Capacity to Promote Glioma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- Lysophosphatidylethanolamine 18:1 drives clear cell renal cell carcinoma by stabilizing SIRT6 to reprogram lipid metabolism.Signal transduction and targeted therapy · 2025Article
- CircPVT1 Promotes Lung Metastasis and Tumor Progression in Renal Cell Carcinoma by Encoding the cP104aa Peptide and Targeting EIF4A3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Metabolomic Understanding of variable risk factors for kidney cancer: a two-sample Mendelian randomization study.Discover oncology · 2025Article
- CircABCA1 promotes ccRCC by reprogramming cholesterol metabolism and facilitating M2 macrophage polarization through IGF2BP3-mediated stabilization of SCARB1 mRNA.Molecular cancer · 2025Article
- Advanced N-glycoproteomics and proteomics approach revealed sexually dimorphic molecular signatures in primary mouse hepatocyte.Analytical and bioanalytical chemistry · 2025Article
- Circulating bile acid profiles characteristics and the potential predictive role in clear cell renal cell carcinoma progression.BMC nephrology · 2025Article
- The perspective of targeting cancer cell metabolism: combination therapy approaches.Molecular biology reports · 2025Review
- Review
- Glutamine metabolism and ammonia death: targeted modulation for enhanced cancer immunotherapy.Frontiers in immunology · 2025Review
- Metabolic Reprogramming in Urological Tumors: New Perspectives from Tumor Metabolic Phenotypes to Therapeutic Targets.International journal of biological sciences · 2025Review
- PHF8/KDM7B: A Versatile Histone Demethylase and Epigenetic Modifier in Nervous System Disease and Cancers.Epigenomes · 2024Review
- Identification of PI3K-AKT Pathway-Related Genes and Construction of Prognostic Prediction Model for ccRCC.Cancer reports (Hoboken, N.J.) · 2024Article
- Glutamine Metabolism and Prostate Cancer.Cancers · 2024Review
- Acetylation- and ubiquitination-regulated SFMBT2 acts as a tumor suppressor in clear cell renal cell carcinoma.Biology direct · 2024Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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