ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Dietary Palmitic Acid Drives a Palmitoyltransferase ZDHHC15-YAP Feedback Loop Promoting Tumor Metastasis.
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 15 papers.
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Who cites it
15 citing papers in PubMed.
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Adipocyte-Derived Palmitic Acid Promotes Breast Cancer Malignancy via ZDHHC15-Mediated S-Palmitoylation of PPARγ.Cancer science · 2026Article
- SMAD4 Palmitoylation Drives a Metabolic-Transcriptional Circuit to Promote Tumorigenesis and Confers Radiosensitivity in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanisms of fatty acid metabolism in tumor metastasis and targeted therapeutic strategies.Discover oncology · 2026Review
- YAP1 in control: how RNA networks and protein modifications shape its function and therapeutic targetability.Molecular cancer · 2026Review
- LifelongNutrients · 2026Article
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- Neutrophil Extracellular Trap Reprograms Cancer Metabolism to Form a Metastatic Niche Promoting Non-Small Cell Lung Cancer Brain Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Scoparone-Induced Phase Separation of ZDHHC12 Drives Ferroptosis via ATG12 S-palmitoylation and Ferritinophagy in Liver Fibrosis.Research (Washington, D.C.) · 2026Article
- Prediction of Esterification and Antioxidant Properties of Food-Derived Fatty Acids and Ascorbic Acid Based on Machine Learning: A Review.Foods (Basel, Switzerland) · 2025Review
- Oleate activates PLD2 lipase and GEF activity by modulating membrane microdomain dynamics via S-acylation.Journal of lipid research · 2025Article
- Stabilization of FASN by USP5-mediated deubiquitination promotes hepatocellular carcinoma progression.Oncogenesis · 2025Article
- A novel zinc finger protein gene signature for prognostic prediction, tumor microenvironment characterization, and therapeutic response in uterine corpus endometrial carcinoma.Scientific reports · 2025Article
- Dietary Palmitic Acid Drives a Palmitoyltransferase ZDHHC15-YAP Feedback Loop Promoting Tumor Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
11 authors.
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Abstract
Elevated uptake of saturated fatty acid palmitic acid (PA) is associated with tumor metastasis; however, the precise mechanisms remain partially understood, hindering the development of therapy for PA-driven tumor metastasis. The Hippo-Yes-associated protein (Hippo/YAP) pathway is implicated in cancer progression. Here it is shown that a high-palm oil diet potentiates tumor metastasis in murine xenografts in part through YAP. It is found that the palmitoyltransferase ZDHHC15 is a YAP-regulated gene that forms a feedback loop with YAP. Notably, PA drives the ZDHHC15-YAP feedback loop, thus enforces YAP signaling, and hence promotes tumor metastasis in murine xenografts. In addition, it is shown that ZDHHC15 associates with Kidney and brain protein (KIBRA, also known as WW- and C2 domain-containing protein 1, WWC1), an upstream component of Hippo signaling, and mediates its palmitoylation. KIBRA palmitoylation leads to its degradation and regulates its subcellular localization and activity toward the Hippo/YAP pathway. Moreover, PA enhances KIBRA palmitoylation and degradation. It is further shown that combinatorial targeting of YAP and fatty acid synthesis exhibits augmented effects against metastasis formation in mice fed with a Palm diet. Collectively, these findings uncover a ZDHHC15-YAP feedback loop as a previously unrecognized mechanism underlying PA-promoted tumor metastasis and support targeting YAP and fatty acid synthesis as potential therapeutic targets in PA-driven tumor metastasis.
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