ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
HDAC8 Enhances the Function of HIF-2α by Deacetylating ETS1 to Decrease the Sensitivity of TKIs in ccRCC.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Molecular Glue cc-885 Inhibits VHL-Deficient Clear Cell Renal Cell Carcinoma via ETS1 Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tumor-Resident Streptococcus pneumoniae Promotes Malignant Progression and Pazopanib Resistance in Clear Cell Renal Cell Carcinoma.Cancer research · 2026Article
- ODF3B Promotes the Progression of Clear Cell Renal Cell Carcinoma via the JAK/STAT Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2026Article
- CA9-Targeted Liposomal Delivery of siETS1 Inhibits Clear Cell Renal Cell Carcinoma Progression by Disrupting the ETS1/MYC Regulatory Axis.International journal of nanomedicine · 2026Article
- Melatonin Suppresses NLRP3 Inflammasome Activation via SIRT1-Mediated ETS1 Deacetylation to Attenuate LPS-Induced Pyroptosis in Alveolar Epithelial Cells.Journal of inflammation research · 2026Article
- Article
- ZDHHC12 Palmitoylates HDAC8 to Promote the Progression of Hepatocellular Carcinoma Associated with a Diet High in Saturated Fatty Acids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Review
- MTFR1 phosphorylation-activated adaptive mitochondrial fusion is essential for colon cancer cell survival during glucose deprivation.Neoplasia (New York, N.Y.) · 2025Article
- ETS1-Driven Nucleolar Stress Orchestrates OLR1Human mutation · 2025Article
- Recent progress on tyrosine kinase inhibitors resistance in renal cell carcinoma: another brick in the wall?Cancer drug resistance (Alhambra, Calif.) · 2025Review
- HIF-2α inhibitors in clear cell renal cell carcinoma: a clinical pharmacy perspective on lipid metabolism, therapeutic management, and resistance strategies.Frontiers in medicine · 2025Review
- Prognostic biomarker and clinical significance of PLOD gene family in clear cell renal cell carcinoma.Frontiers in oncology · 2025Article
- Dephosphorylation-related signature predicts the prognosis of papillary renal cell carcinoma.Translational cancer research · 2024Article
- HDAC8 Enhances the Function of HIF-2α by Deacetylating ETS1 to Decrease the Sensitivity of TKIs in ccRCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
10 authors.
Funding
Abstract
Drug resistance after long-term use of Tyrosine kinase inhibitors (TKIs) has become an obstacle for prolonging the survival time of patients with clear cell renal cell carcinoma (ccRCC). Here, genome-wide CRISPR-based screening to reveal that HDAC8 is involved in decreasing the sensitivity of ccRCC cells to sunitinib is applied. Mechanically, HDAC8 deacetylated ETS1 at the K245 site to promote the interaction between ETS1 and HIF-2α and enhance the transcriptional activity of the ETS1/HIF-2α complex. However, the antitumor effect of inhibiting HDAC8 on sensitized TKI is not very satisfactory. Subsequently, inhibition of HDAC8 increased the expression of NEK1, and up-regulated NEK1 phosphorylated ETS1 at the T241 site to promote the interaction between ETS1 and HIF-2α by impeded acetylation at ETS1-K245 site is showed. Moreover, TKI treatment increased the expression of HDAC8 by inhibiting STAT3 phosphorylation in ccRCC cells is also found. These 2 findings highlight a potential mechanism of acquired resistance to TKIs and HDAC8 inhibitors in ccRCC. Finally, HDAC8-in-PROTACs to optimize the effects of HDAC8 inhibitors through degrading HDAC8 and overcoming the resistance of ccRCC to TKIs are synthesized. Collectively, the results revealed HDAC8 as a potential therapeutic candidate for resistance to ccRCC-targeted therapies.
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