ArticleeLife2023
A positive feedback loop between ZEB2 and ACSL4 regulates lipid metabolism to promote breast cancer metastasis.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 16 citations in OpenAlex.
- Metabolic determinants of autoimmune kidney diseases.Nature reviews. Nephrology · 2026Review
- Unlocking the ferroptotic window: Lipidomic rewiring and metabolic addiction in EMT-driven breast cancer resistance.Cell death discovery · 2026Review
- [ZEB2 promotes glioblastoma progression by reprogramming lipid metabolism through the CYLD/FASN axis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Bidirectional Feedback Between Metabolic Reprogramming and Epithelial-Mesenchymal Transition: From Mechanisms to Therapeutic Interventions.Molecules (Basel, Switzerland) · 2026Review
- An ERRα-ZEB1 transcriptional signature predicts survival in triple-negative breast cancers.Molecular medicine (Cambridge, Mass.) · 2026Article
- Mechanisms of fatty acid metabolism in tumor metastasis and targeted therapeutic strategies.Discover oncology · 2026Review
- Metabolic crosstalk among cancer-associated fibroblasts, adipocytes and immune cells as an immunosuppressive tumor microenvironment driver.Experimental & molecular medicine · 2026Review
- Cancer neuroscience: signaling pathways and new therapeutic strategies for cancer.Signal transduction and targeted therapy · 2026Review
- Acyl-CoA Synthetase Long-Chain Family Member 4 in Liver Injury: Multidimensional Regulation and Therapeutic Potential.Gastroenterology research · 2026Review
- Molecular and Immune Mechanisms Governing Cancer Metastasis, Including Dormancy, Microenvironmental Niches, and Tumor-Specific Programs.International journal of molecular sciences · 2026Review
- Membrane Stress and Ferroptosis: Lipid Dynamics in Cancer.International journal of molecular sciences · 2026Review
- Lipid remodeling and ferroptosis in phosphatidylcholine-mediated tumor-stroma crosstalk.Frontiers in molecular biosciences · 2026Review
- Epitranscriptomic regulation via m6A RNA modification in PCOS pathophysiology.Molecular biology reports · 2025Review
- GLP-1R associates with VAPB and SPHKAP at ERMCSs to regulate β-cell mitochondrial remodelling and function.Nature communications · 2025Article
- Role of lipid droplets in pulmonary arterial hypertension: focusing on pulmonary artery smooth muscle cell proliferation.Lipids in health and disease · 2025Review
- Lipid Metabolism Reprogramming in Cancer: Insights into Tumor Cells and Immune Cells Within the Tumor Microenvironment.Biomedicines · 2025Review
- Analyzing the Blueprint: Exploring the Molecular Profile of Metastasis and Therapeutic Resistance.International journal of molecular sciences · 2025Review
- Bi-directional metabolic reprogramming between cancer cells and T cells reshapes the anti-tumor immune response.PLoS biology · 2025Article
- The Splice Variant of the NCOR2 Gene BQ323636.1 Modulates ACSL4 Expression to Enhance Fatty Acid Metabolism and Support of Tumor Growth in Breast Cancer.International journal of molecular sciences · 2025Article
- Transcription factor ZNF266 suppresses cancer progression by modulating CA9-mediated intracellular pH alteration in lung adenocarcinoma.Respiratory research · 2025Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Lipid metabolism plays a critical role in cancer metastasis. However, the mechanisms through which metastatic genes regulate lipid metabolism remain unclear. Here, we describe a new oncogenic-metabolic feedback loop between the epithelial-mesenchymal transition transcription factor ZEB2 and the key lipid enzyme ACSL4 (long-chain acyl-CoA synthetase 4), resulting in enhanced cellular lipid storage and fatty acid oxidation (FAO) to drive breast cancer metastasis. Functionally, depletion of ZEB2 or ACSL4 significantly reduced lipid droplets (LDs) abundance and cell migration. ACSL4 overexpression rescued the invasive capabilities of the ZEB2 knockdown cells, suggesting that ACSL4 is crucial for ZEB2-mediated metastasis. Mechanistically, ZEB2-activated ACSL4 expression by directly binding to the ACSL4 promoter. ACSL4 binds to and stabilizes ZEB2 by reducing ZEB2 ubiquitination. Notably, ACSL4 not only promotes the intracellular lipogenesis and LDs accumulation but also enhances FAO and adenosine triphosphate production by upregulating the FAO rate-limiting enzyme CPT1A (carnitine palmitoyltransferase 1 isoform A). Finally, we demonstrated that ACSL4 knockdown significantly reduced metastatic lung nodes in vivo. In conclusion, we reveal a novel positive regulatory loop between ZEB2 and ACSL4, which promotes LDs storage to meet the energy needs of breast cancer metastasis, and identify the ZEB2-ACSL4 signaling axis as an attractive therapeutic target for overcoming breast cancer metastasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.