ArticleEMBO molecular medicine2024
FADS1/2 control lipid metabolism and ferroptosis susceptibility in triple-negative breast cancer.
Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed.
- A Ferrous-Supply-Regenerating Lipid Nanoparticle Integrating RNAi Induces Ferroptosis for Cancer Therapy.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- [Overexpression of miR-183-5p enhances malignant phenotype and inhibits ferroptosis of triple-negative breast cancer cells by negatively regulating KLHL24].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Evolutionary conservation analysis reveals a primordial function of STING as a regulator of lipid metabolism via FADS2.Nature communications · 2026Article
- Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Target FADS1-arachidonic acid-ferroptosis axis: A metabolic bridge linking matrix stiffness to PDAC stemness.Materials today. Bio · 2026Article
- Opposing roles of DGAT-mediated lipid droplet biogenesis in the regulation of ferroptosis sensitivity.The FEBS journal · 2026Article
- FADS1-mediated Efferocytosis in Tumor-Associated Macrophages Shapes an Immunosuppressive Microenvironment in Gastric Cancer.Cellular and molecular life sciences : CMLS · 2026Article
- Intrinsic polyunsaturated fatty acid synthesis capacity dictates ferroptosis sensitivity under restricted arachidonic acid availability.Cell death discovery · 2026Article
- LMAN2 promotes breast cancer progression and deduces cell sensitivity to doxorubicin through stearoyl-CoA desaturase.Breast cancer research : BCR · 2026Article
- Ferroptosis as an approach to leverage cancer metabolism.Trends in cell biology · 2026Review
- Stearoyl-CoA desaturase 1 integrates tissue-specific oncogenic pathways into a pan-cancer ferroptosis resistance program.Cell death & disease · 2026Review
- Targeting the lipid desaturation network in cancer: from metabolic plasticity to precision therapeutics.Journal of experimental & clinical cancer research : CR · 2026Review
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Red blood cell-derived extracellular vesicles enable cisplatin and cetuximab combined therapy against triple-negative breast cancer.Journal of nanobiotechnology · 2026Article
- The biphasic interactions between ferroptosis and oxidative stress: from molecular mechanisms to disease interventions.Molecular biology reports · 2026Review
- Ferroptosis in breast cancer: From adipocyte-immune-iron regulation to therapeutic application.Clinical and translational medicine · 2026Review
- Ascites protects against ferroptosis and enables the peritoneal growth of ovarian cancer.Nature communications · 2026Article
- Integrating single-cell RNA and bulk RNA sequencing data to identify prognostic genes associated with pyrimidine metabolism in triple-negative breast cancer by machine learning algorithm combinations.Discover oncology · 2026Article
- Ferroptosis in Breast Cancer: Molecular Insights and Therapeutic Strategies.Frontiers in bioscience (Landmark edition) · 2026Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors.
Funding
Abstract
Triple-negative breast cancer (TNBC) has limited therapeutic options, is highly metastatic and characterized by early recurrence. Lipid metabolism is generally deregulated in TNBC and might reveal vulnerabilities to be targeted or used as biomarkers with clinical value. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation which is facilitated by the presence of polyunsaturated fatty acids (PUFA). Here we identify fatty acid desaturases 1 and 2 (FADS1/2), which are responsible for PUFA biosynthesis, to be highly expressed in a subset of TNBC with a poorer prognosis. Lipidomic analysis, coupled with functional metabolic assays, showed that FADS1/2 high-expressing TNBC are susceptible to ferroptosis-inducing agents and that targeting FADS1/2 by both genetic interference and pharmacological approach renders those tumors ferroptosis-resistant while unbalancing PUFA/MUFA ratio by the supplementation of exogenous PUFA sensitizes resistant tumors to ferroptosis induction. Last, inhibiting lipid droplet (LD) formation and turnover suppresses the buffering capacity of LD and potentiates iron-dependent cell death. These findings have been validated in vitro and in vivo in mouse- and human-derived clinically relevant models and in a retrospective cohort of TNBC patients.
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