ArticleCancer research2023
ZDHHC2-Mediated AGK Palmitoylation Activates AKT-mTOR Signaling to Reduce Sunitinib Sensitivity in Renal Cell Carcinoma.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 69 citations in OpenAlex.
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- Associations of host gene expression in the brain, liver, muscle with fecal and cecal microbiota composition in pigs.Functional & integrative genomics · 2026Article
- Pan-Cancer Multi-Omics Analysis Reveals the Potential of ZDHHC16 in Tumor Progression and Immune Regulation.Chemical biology & drug design · 2026Article
- Acylglycerol kinase contributes to cell proliferation by activating NF‑κB signaling pathway in pancreatic cancer.Oncology reports · 2026Article
- ABHD17C-Mediated S-Depalmitoylation of BCL6B Enhances CD24 Transcription to Resist Macrophage Phagocytosis in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Overcoming mTOR Inhibitor Resistance: From Biological Basis to Therapeutic Strategies.Biomedicines · 2026Review
- ZDHHC9-Mediated Palmitoylation of ACSL4 Drives Ferroptosis in Diabetes Mellitus-Induced Erectile Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CAIX-targeted radiotracer for diagnosis and monitoring VEGFR-TKI response in clear cell renal cell carcinoma.European journal of nuclear medicine and molecular imaging · 2026Article
- Exploring the functional role of palmitoylation genes in clear cell renal cell carcinoma and their impact on tumor microenvironment.BMC genomic data · 2026Article
- Two decades of research on drug resistance in renal cell carcinoma.Discover oncology · 2026Article
- ZDHHC14-driven RUNX2 S-palmitoylation attenuates ferroptosis and enhances chemoresistance in ovarian cancer via the YAP1/GLS1 axis.Apoptosis : an international journal on programmed cell death · 2026Article
- Tumor-Resident Streptococcus pneumoniae Promotes Malignant Progression and Pazopanib Resistance in Clear Cell Renal Cell Carcinoma.Cancer research · 2026Article
- Epigenetically silenced KAT2B suppresses de novo lipogenesis through destroying HDAC5/LSD1 complex assembly in renal cell carcinoma.Journal of advanced research · 2026Article
- PABPC1-induced stabilization of PGK1 mRNA reduces apoptosis and sunitinib sensitivity in renal cell carcinoma by suppressing endoplasmic reticulum stress.Cell death & disease · 2026Article
- Targeting the ZDHHC9-mediated STAT1 palmitoylation-phosphorylation conversion inhibits gastric cancer progression.Journal of gastroenterology · 2026Article
- Expression of PSTPIP1 in Renal Cell Carcinoma and Its Prognostic Value.Biochemical genetics · 2026Article
- Palmitoylation in Renal Physiology and Pathology.Biomolecules · 2026Review
- Multi-omics analysis suggests ZDHHC18 as a potential risk factor for clear cell renal cell carcinoma linked to myeloid DC morphology.Discover oncology · 2026Article
- Preliminary exploration of the putative function of SF3A2 in clear cell renal cell carcinoma.Molecular medicine reports · 2026Article
- Improving erectile function in diabetic male mice by rescuing depalmitoylated FBP1 to reduce cavernosal lactate.Nature communications · 2026Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine kinase inhibitors (TKI) that can suppress the VEGF signaling pathway and angiogenesis have been developed to impede the progression of malignant tumors and have been approved as first-line targeted agents for clear cell renal cell carcinoma (ccRCC). Dysregulation of lipid metabolism is a major driver of TKI resistance in renal cancer. In this study, we showed that the palmitoyl acyltransferase ZDHHC2 is abnormally upregulated in tissues and cell lines resistant to TKIs, such as sunitinib. Upregulation of ZDHHC2 contributed to sunitinib resistance in cells and mice, and ZDHHC2 regulated angiogenesis and cell proliferation in ccRCC. Mechanistically, ZDHHC2 mediated AGK S-palmitoylation to promote translocation of AGK into the plasma membrane and activation of the PI3K-AKT-mTOR signaling pathway in ccRCC, which modulated sunitinib sensitivity. In conclusion, these results identify a ZDHHC2-AGK signaling axis and suggest that ZDHHC2 is a targetable candidate for improving the antitumor efficacy of sunitinib in ccRCC. SIGNIFICANCE: ZDHHC2 confers sunitinib resistance to clear cell renal cell carcinoma by catalyzing AGK palmitoylation to activate the AKT-mTOR pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.