ArticleCancer research2025
Lipid Composition Alters Ferroptosis Sensitivity.
Article in Cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Dystrophin Deficiency Creates a Pro-Ferroptotic Environment in Diaphragm of mdx Mice That Is Modified by Diet and Glucocorticoid Treatment.Biomolecules · 2026Article
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Ketogenic Diet as an Adjuvant in Epithelial Cancers: Mechanisms, Model Systems, and Translational Opportunities.Cancers · 2026Review
- Reconstituted phospholipid membrane-coated FeBioactive materials · 2026Article
- Double-bond geometry determines fatty acid metabolic fate and ferroptosis sensitivity.bioRxiv : the preprint server for biology · 2026Article
- Ferroptosis Resistance: Redundant Antioxidant Networks Are a Barrier to Cancer Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Regulated cell death: a multidimensional regulatory network in the pathogenesis of renal fibrosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Review
- The role of estrogen and its receptors in the regulation of ferroptosis and autophagy.Molecular biology reports · 2026Review
- Fat bolsters tumours against ferroptosis.Nature cell biology · 2026Article
- Iron overload disrupts lipid desaturation through SKN-1 signaling inMaterials today. Bio · 2026Article
- Review
- Systematic Evaluation Defines the Limits of Ferroptosis in Cancer Therapy.bioRxiv : the preprint server for biology · 2026Article
- Targeting Metabolic Vulnerabilities in Glioblastoma: a Framework for Multi-node Combination Therapy.Current oncology reports · 2026Review
- Ferroptosis surveillance: Insights fromFerroptosis and oxidative stress · 2026Article
- Targeting ferroptosis in lung cancer: pharmacological regulation, nanomedicine-based delivery, and AI-enabled translational strategies.American journal of cancer research · 2026Review
- Beyond angiogenesis: integrating ferroptosis and metabolic rewiring for next-generation RCC therapy.Frontiers in oncology · 2026Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Ferroptosis is a regulated nonapoptotic cell death process characterized by iron-dependent lipid peroxidation. Peroxidation of polyunsaturated fatty acid-containing phospholipids (PUFA-PL) is necessary for the execution of ferroptosis. Glutathione peroxidase 4 (GPX4) suppresses ferroptosis by reducing lipid hydroperoxides to lipid alcohols. GPX4 may be a useful target for drug development, highlighting the need to identify factors that govern GPX4 inhibitor sensitivity. In this study, we found that reduced GPX4 expression was sufficient to induce ferroptosis in multiple adherent (2D) cancer cell cultures. However, lower GPX4 protein levels did not consistently affect tumor xenograft growth in mice. Culturing cells as spheroids (3D) was sufficient to reduce sensitivity to pharmacologic GPX4 inhibition. Mechanistically, growth in 3D versus 2D conditions upregulated expression of the monounsaturated fatty acid (MUFA) biosynthetic gene stearoyl-CoA desaturase, altering the ratio of MUFA-PLs to PUFA-PLs in a direction favoring ferroptosis resistance. Similar shifts in MUFA-PL:PUFA-PL ratios were observed in xenograft tumors. Thus, lipidome remodeling in 3D growth conditions and in vivo may limit GPX4 inhibitor efficacy. SIGNIFICANCE: Changes in lipid composition can affect induction of ferroptosis, explaining why sensitivity of cancer cells in tissue culture does not reliably translate to more complex models and suggesting potential ferroptosis sensitization strategies.
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