ArticleCancer research2022
HDAC5 Loss Enhances Phospholipid-Derived Arachidonic Acid Generation and Confers Sensitivity to cPLA2 Inhibition in Pancreatic Cancer.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- Nuciferine Suppresses Inflammatory Hepatocarcinogenesis by Targeting cPLA2-Dependent Arachidonic Acid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Epigenetically silenced KAT2B suppresses de novo lipogenesis through destroying HDAC5/LSD1 complex assembly in renal cell carcinoma.Journal of advanced research · 2026Article
- Histone deacetylases: Function in tumor development and therapeutic prospects (Review).Oncology letters · 2026Review
- The Role of Protein Kinases in the Management of Oncological Diseases by Acting on Ferroptotic Pathways.International journal of molecular sciences · 2026Review
- HDAC5 stabilization by tubeimoside I suppresses cervical cancer metastasis via inhibiting H3K27ac/KPNA2 axis.British journal of cancer · 2026Article
- HDAC5 deficiency induces intrinsic resistance to KRAS inhibition by disrupting c-Myc acetylation-ubiquitination homeostasis.The Journal of clinical investigation · 2026Article
- Piezo1 activation in endothelial cells aggravates microvascular ischemia-reperfusion injury in limbs by enhancing ferroptosis.Experimental & molecular medicine · 2026Article
- CK2-mediated HDAC5 shuttling regulates DNA end resection through Ku70 deacetylation.Theranostics · 2026Article
- Association of HPGDS Expression with Prognosis and Immune Microenvironment Remodeling in Pancreatic Cancer.Cancer management and research · 2026Article
- Salidroside alleviates the progression of idiopathic pulmonary fibrosis by regulating ferroptosis.Cytotechnology · 2025Article
- The role of phosphatidylcholine metabolism in tumors.Medical oncology (Northwood, London, England) · 2025Review
- CCT196969 inhibits TNBC by targeting the HDAC5/RXRA/ASNS axis to down-regulate asparagine synthesis.Journal of experimental & clinical cancer research : CR · 2025Article
- Mendelian randomization analysis of gut microbiota-immune cell interactions in malignant neoplasm of nasopharynx.AMB Express · 2025Article
- LPCAT3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acid.Translational oncology · 2025Article
- TRIM21 Promotes Tumor Growth and Gemcitabine Resistance in Pancreatic Cancer by Inhibiting EPHX1-Mediated Arachidonic Acid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Arachidonic acid metabolism as a novel pathogenic factor in gastrointestinal cancers.Molecular and cellular biochemistry · 2025Review
- Determination of nine prostaglandins in the arachidonic acid metabolic pathway with UHPLC-QQQ-MS/MS and application toFrontiers in pharmacology · 2025Article
- Banxia-Xiexin Decoction Ameliorates Colitis-Associated Colorectal Cancer by Modulating Inflammatory Responses and the Complement and Coagulation Cascade Pathway.Journal of inflammation research · 2025Article
- Arachidonic acid metabolism in health and disease.MedComm · 2023Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HDAC5 is a class IIa histone deacetylase member that is downregulated in multiple solid tumors, including pancreatic cancer, and loss of HDAC5 is associated with unfavorable prognosis. In this study, assessment of The Cancer Genome Atlas pancreatic adenocarcinoma dataset revealed that expression of HDAC5 correlates negatively with arachidonic acid (AA) metabolism, which has been implicated in inflammatory responses and cancer progression. Nontargeted metabolomics analysis revealed that HDAC5 knockdown resulted in a significant increase in AA and its downstream metabolites, such as eicosanoids and prostaglandins. HDAC5 negatively regulated the expression of the gene encoding calcium-dependent phospholipase A2 (cPLA2), the key enzyme in the production of AA from phospholipids. Mechanistically, HDAC5 repressed cPLA2 expression via deacetylation of GATA1. HDAC5 knockdown in cancer cells enhanced sensitivity to genetic or pharmacologic inhibition of cPLA2 in vitro and in vivo. Fatty acid supplementation in the diet reversed the sensitivity of HDAC5-deficient tumors to cPLA2 inhibition. These data indicate that HDAC5 loss in pancreatic cancer results in the hyperacetylation of GATA1, enabling the upregulation of cPLA2, which contributes to overproduction of AA. Dietary management plus cPLA2-targeted therapy could serve as a viable strategy for treating HDAC5-deficient pancreatic cancer patients. SIGNIFICANCE: The HDAC5-GATA1-cPLA2-AA signaling axis regulates sensitivity to fat restriction plus cPLA2 inhibition in pancreatic ductal adenocarcinoma, proposing dietary management as a feasible strategy for treating a subset of patients with pancreatic cancer.
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Registered trials
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