ArticleEBioMedicine2019
NKX2-8 deletion-induced reprogramming of fatty acid metabolism confers chemoresistance in epithelial ovarian cancer.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Current hotspots and trends in cancer metabolic reprogramming: a scientometric analysis.Frontiers in immunology · 2024Pooled it
- Shared Major Metabolic Pathways and Potential Targeted Therapies in Malignancies and Systemic Lupus Erythematosus.Biomolecules · 2026Review
- Fatty acid metabolic reprogramming in the tumor microenvironment: Unraveling mechanisms and therapeutic prospects.Genes & diseases · 2026Review
- Platinum-resistant ovarian cancer: From mechanisms to treatment strategies.Genes & diseases · 2026Review
- Acylcarnitines in Cancer Metabolism: Mechanistic Insights and Stratification Potential.Cancers · 2026Review
- Novel therapeutic strategies for targeting fatty acid oxidation in cancer.Biomarker research · 2025Review
- Targeting Mitochondrial Cholesterol Efflux via TCF21/ABCA10 Pathway to Enhance Cisplatin Efficacy in Ovarian Cancer.Biochemical genetics · 2025Article
- Emerging roles for fatty acid oxidation in cancer.Genes & diseases · 2025Review
- Alectinib and SALL4-Targeted Fatty Acid Oxidation: A Strategy to Combat Oxaliplatin Resistance in Gastric Cancer.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025Article
- The role and mechanism of fatty acid oxidation in cancer drug resistance.Cell death discovery · 2025Review
- Review
- ZNF468-mediated epigenetic upregulation of VEGF-C facilitates lymphangiogenesis and lymphatic metastasis in ESCC via PI3K/Akt and ERK1/2 signaling pathways.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Succinylation of 14-3-3 theta by CPT1A promotes survival and paclitaxel resistance in nasal type extranodal natural killer/T-cell lymphoma.Translational oncology · 2024Article
- Recent advances in the potential role of RNA N4-acetylcytidine in cancer progression.Cell communication and signaling : CCS · 2024Review
- Article
- Joint analysis of the metabolomics and transcriptomics uncovers the dysregulated network and develops the diagnostic model of high-risk neuroblastoma.Scientific reports · 2023Article
- Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics.Journal of hematology & oncology · 2023Review
- NK2 homeobox gene cluster: Functions and roles in human diseases.Genes & diseases · 2023Review
- Perhexiline: Old Drug, New Tricks? A Summary of Its Anti-Cancer Effects.Molecules (Basel, Switzerland) · 2023Review
- Hydropersulfides (RSSH) attenuate doxorubicin-induced cardiotoxicity while boosting its anticancer action.Redox biology · 2023Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAberrant fatty acid (FA) metabolism is a unique vulnerability of cancer cells and may present a promising target for cancer therapy. Our study aims to elucidate the molecular mechanisms by which NKX2-8 deletion reprogrammed FA metabolism-induced chemoresistance in epithelial ovarian cancer (EOC).
methodsThe deletion frequency and expression of NKX2-8 in 144 EOC specimens were assayed using Fluorescence in situ hybridization and immunochemical assays. The effects of NKX2-8 deletion and the fatty acid oxidation (FAO) antagonist Perhexiline on chemoresistance were examined by Annexin V and colony formation in vitro, and via an intraperitoneal tumor model in vivo. The mechanisms of NKX2-8 deletion in reprogrammed FA metabolism was determined using Chip-seq, metabolomic analysis, FAO assays and immunoprecipitation assays.
findingsNKX2-8 deletion was correlated with the overall and relapse-free survival of EOC patients. NKX2-8 inhibited the FAO pathway by epigenetically suppressing multiple key components of the FAO cascade, including CPT1A and CPT2. Loss of NKX2-8 resulted in reprogramming of FA metabolism of EOC cells in an adipose microenvironment and leading to platinum resistance. Importantly, pharmacological inhibition of FAO pathway using Perhexiline significantly counteracted NKX2-8 deletion-induced chemoresistance and enhanced platinum's therapeutic efficacy in EOC.
interpretationOur results demonstrate that NKX2-8 deletion-reprogrammed FA metabolism contributes to chemoresistance and Perhexiline might serve as a potential tailored treatment for patients with NKX2-8-deleted EOC. FUND: This work was supported by Natural Science Foundation of China; Guangzhou Science and Technology Plan Projects; Natural Science Foundation of Guangdong Province; The Fundamental Research Funds for the Central Universities.
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