ArticleCell communication and signaling : CCS2024
ZDHHC5-mediated S-palmitoylation of FAK promotes its membrane localization and epithelial-mesenchymal transition in glioma.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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26 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Research trends of protein palmitoylation in cancer from 2004 to 2024: a bibliometric and visualization analysis.Frontiers in oncology · 2025Pooled it
- Article
- ZDHHC5: a pivotal palmitoyltransferase orchestrating signaling networks - unraveling mechanisms and therapeutic horizons.Biomarker research · 2026Review
- Palmitoylation-mediated regulation of KAT2A promotes lung metastasis in breast cancer.Nature cell biology · 2026Article
- The Emerging Roles of Protein Lipidation in Fertility and Reproductive Disorders: Mechanisms and Therapeutic Implications.Biomolecules · 2026Review
- Prognostic value of palmitoylation-regulated mechanisms in glioblastoma: integrated multi-omics analysis via least absolute shrinkage and selection operator (LASSO) regression and single-cell sequencing.Translational cancer research · 2026Article
- Targeting the exosomal CaMK2A-ZDHHC3-GPX4 pathway reprograms tumor-associated macrophages and enhances anti-PD-1/PD-L1 immunotherapy in gastric cancer.International journal of biological sciences · 2026Article
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- Transcriptomics, identification, and testing of manganese metabolism-related genes in cervical squamous cell carcinoma.Frontiers in oncology · 2026Article
- Bioinformatics Analysis of ZDHHC-protein Acyltransferase for Predicting the Rupture of Aneurysmal Subarachnoid Hemorrhage.Current neurovascular research · 2026Article
- Bridging metabolic reprogramming and targeted therapy: the critical role of S-palmitoylation in cancer.Frontiers in cell and developmental biology · 2026Review
- Development and validation of a novel palmitoylation-related prognostic signature in head and neck squamous cell carcinoma.Translational cancer research · 2025Article
- S-palmitoylation-related genes in Crohn's disease: Bioinformatic identification and validation.Biomolecules & biomedicine · 2025Article
- Role of S-palmitoylation in digestive system diseases.Cell death discovery · 2025Review
- Single-cell transcriptome sequencing reveals new epithelial-stromal associated mesenchymal-like subsets in recurrent gliomas.Acta neuropathologica communications · 2025Article
- Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.International journal of cardiology. Heart & vasculature · 2025Review
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- Recent Overview of Protein Palmitoylation and Profiling Methodologies.Methods in molecular biology (Clifton, N.J.) · 2025Review
- ZDHHC5 as a central regulator in a palmitoylation-associated prognostic model for lung adenocarcinoma: insights from pan-cancer and experimental analyses.Frontiers in immunology · 2025Article
- Comprehensive analysis of palmitoylation-related proteins for prognostic risk evaluation and tumor immune microenvironment assessment in glioma.Frontiers in immunology · 2025Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundAbnormal activation of FAK is associated with tumor development and metastasis. Through interactions with other intracellular signalling molecules, FAK influences cytoskeletal remodelling, modulation of adhesion signalling, and activation of transcription factors, promoting migration and invasion of tumor cells. However, the exact mechanism that regulates these processes remains unresolved. Herein, our findings indicate that the S-palmitoylation of FAK is crucial for both its membrane localization and activation.
methodsThe palmitoylation of FAK in U251 and T98G cells was assessed by an acyl-PEG exchange (APE) assay and a metabolic incorporation assay. Cellular palmitoylation was inhibited using 2-bromopalmitate, and the palmitoylation status and cellular localization of FAK were determined. A metabolic incorporation assay was used to identify the potential palmitoyl acyltransferase and the palmitoylation site of FAK. Cell Counting Kit-8 (CCK8) assays, colony formation assays, and Transwell assays were conducted to assess the impact of ZDHHC5 in GBM. Additionally, intracranial GBM xenografts were utilized to investigate the effects of genetically silencing ZDHHC5 on tumor growth.
resultsInhibiting FAK palmitoylation leads to its redistribution from the membrane to the cytoplasm and a decrease in its phosphorylation. Moreover, ZDHHC5, a protein-acyl-transferase (PAT), catalyzes this key modification of FAK at C456. Knockdown of ZDHHC5 abrogates the S-palmitoylation and membrane distribution of FAK and impairs cell proliferation, invasion, and epithelial-mesenchymal transition (EMT). Taken together, our research reveals the crucial role of ZDHHC5 as a PAT responsible for FAK S-palmitoylation, membrane localization, and activation.
conclusionsThese results imply that targeting the ZDHHC5/FAK axis has the potential to be a promising strategy for therapeutic interventions for glioblastoma (GBM). Video Abstract.
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