ArticleNature cell biology2024
Zeb1 mediates EMT/plasticity-associated ferroptosis sensitivity in cancer cells by regulating lipogenic enzyme expression and phospholipid composition.
Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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Who cites it
116 citing papers in PubMed.
- Ferroptosis and tumor microenvironment: orchestrating therapy resistance, immune evasion, and metastatic events.Medical oncology (Northwood, London, England) · 2026Review
- Targeted extracellular degradation of LRP8 promotes ferroptosis in cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Decoding epithelial-mesenchymal transitions with multi-omics.Nature reviews. Genetics · 2026Review
- Metabolites and cancer metastasis.Oncogene · 2026Review
- Ferroptotic propagation: from single-cell execution to tissue-scale death programs.Cell research · 2026Review
- Lipid metabolic reprogramming of tumor-associated macrophages drives resistance to immune checkpoint blockade in lung cancer: a narrative review of mechanisms and therapeutic strategies.Translational lung cancer research · 2026Review
- TRIM26 triggers ferroptosis via ZEB1 degradation to suppress nasopharyngeal carcinoma progression.Journal of molecular histology · 2026Article
- Silencing arachidonate 15-lipoxygenase alleviates hypoxia-induced cognitive impairment through the mediation of phospholipase A2 group IVC-LPC18:0 to suppress ferroptosis.Molecular biomedicine · 2026Article
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- Targeting the CTBP1-CETP axis overcomes ferroptosis resistance in non-small cell lung cancer by altering lipid accumulation.Clinical and translational medicine · 2026Article
- From Ferroptotic Stress to Stemness: TNT-Mediated EMT Plasticity in Cancer Progression.Stem cell reviews and reports · 2026Review
- Long non-coding RNA (lncRNA) XIST drives TGF-β-induced renal cancer progression via miR-141-3p/ZEB1 signaling.Translational andrology and urology · 2026Article
- Multi-omics profiling unveils biological and clinical insights into pulmonary sarcomatoid carcinoma.Cell reports. Medicine · 2026Article
- Double-bond geometry determines fatty acid metabolic fate and ferroptosis sensitivity.bioRxiv : the preprint server for biology · 2026Article
- Piezoelectric Nanozymes With Acoustically Rejuvenated Catalytic Activities Rewire Lipid Metabolism for Two-Pronged Ferroptotic Therapy.Angewandte Chemie (International ed. in English) · 2026Article
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Intrinsic polyunsaturated fatty acid synthesis capacity dictates ferroptosis sensitivity under restricted arachidonic acid availability.Cell death discovery · 2026Article
- Unlocking the ferroptotic window: Lipidomic rewiring and metabolic addiction in EMT-driven breast cancer resistance.Cell death discovery · 2026Review
- Metabolic plasticity and optimal redox homeostasis are essential for efficient metastatic colonization.Molecular metabolism · 2026Article
56 more citing papers are in PubMed but not listed here.
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24 authors.
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Abstract
Therapy resistance and metastasis, the most fatal steps in cancer, are often triggered by a (partial) activation of the epithelial-mesenchymal transition (EMT) programme. A mesenchymal phenotype predisposes to ferroptosis, a cell death pathway exerted by an iron and oxygen-radical-mediated peroxidation of phospholipids containing polyunsaturated fatty acids. We here show that various forms of EMT activation, including TGFβ stimulation and acquired therapy resistance, increase ferroptosis susceptibility in cancer cells, which depends on the EMT transcription factor Zeb1. We demonstrate that Zeb1 increases the ratio of phospholipids containing pro-ferroptotic polyunsaturated fatty acids over cyto-protective monounsaturated fatty acids by modulating the differential expression of the underlying crucial enzymes stearoyl-Co-A desaturase 1 (SCD), fatty acid synthase (FASN), fatty acid desaturase 2 (FADS2), elongation of very long-chain fatty acid 5 (ELOVL5) and long-chain acyl-CoA synthetase 4 (ACSL4). Pharmacological inhibition of selected lipogenic enzymes (SCD and FADS2) allows the manipulation of ferroptosis sensitivity preferentially in high-Zeb1-expressing cancer cells. Our data are of potential translational relevance and suggest a combination of ferroptosis activators and SCD inhibitors for the treatment of aggressive cancers expressing high Zeb1.
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