ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
ZDHHC12 Palmitoylates HDAC8 to Promote the Progression of Hepatocellular Carcinoma Associated with a Diet High in Saturated Fatty Acids.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Emerging roles of α/β hydrolase domain (ABHD) proteins in S-palmitoylation modification: molecular mechanisms, structural features, and pathological implications.Cellular & molecular biology letters · 2026Review
- Integrated multi-omic and functional profiling reveals a ZDHHC16-associated palmitoylation-proteostasis state in hepatocellular carcinoma.Discover oncology · 2026Article
- Advances in Lipid Metabolism Reprogramming in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2026Review
- The functional roles and therapeutic potential of protein palmitoylation in hepatocellular carcinoma.Discover oncology · 2026Review
- PIK3CA Mutations Downregulate PPT1 to Promote Adipogenesis by Suppressing P300 Depalmitoylation and Phase Separation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ZDHHC9 palmitoylates LAMTOR1 to promote renal cell carcinoma malignant progression.Cell death & disease · 2026Article
- Insulin resistance: mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Global surge in pancreatic cancer cases driven by ageing populations and modifiable risks.Journal of global health · 2026Article
- Integrated Pan-Cancer, Single-Cell, and Spatial Transcriptomic Analyses Identify ZDHHC12 as a Biomarker Associated with Macrophage Infiltration and the Immune Landscape in Glioma.Journal of Cancer · 2026Article
- Risk assessment of digestive cancers with the modified EAT-Lancet diet pattern: a prospective cohort study based on UK Biobank.BMC gastroenterology · 2025Article
- A Novel Palmitoylation-Related Molecular Signature for Predicting and Therapeutically Targeting Alzheimer's Disease.Molecular neurobiology · 2025Article
- 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
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8 authors.
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Abstract
Excessive intake of saturated fatty acids (SFAs)-commonly associated with diets rich in fried foods and red meat-significantly increases the risk of hepatocellular carcinoma (HCC). Palmitic acid (PA), the most prevalent type of SFA, is selected as the representative model for this study. Palmitoyltransferases play crucial roles in protein palmitoylation mediated by PA; however, the most significantly altered palmitoyltransferase under high-SFA dietary conditions remains unidentified. This study reveals zinc finger DHHC-type palmitoyltransferase 12 (ZDHHC12) as a key protein in PA-driven HCC progression that functions by stabilizing the oncogenic histone deacetylase 8 (HDAC8). Mechanistically, PA supplementation upregulates ZDHHC12 expression by activating the transcription factor SWI/SNF-related BAF chromatin remodeling complex subunit ATPase 4 (SMARCA4). ZDHHC12 mediates HDAC8 palmitoylation at cysteine 244, thereby inhibiting its lysosomal degradation and ultimately promoting HCC progression. This study reveals that ZDHHC12 is a critical mediator of PA-induced HCC progression and that targeting HDAC8 can suppress this process. These findings offer a potential therapeutic strategy for HCC patients with high dietary intake of SFAs, particularly PA.
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