ArticleJournal of experimental & clinical cancer research : CR2025
FASN inhibits ferroptosis in breast cancer via USP5 palmitoylation-dependent regulation of GPX4 deubiquitination.
Article in Journal of experimental & clinical cancer research : CR, 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.
- Dual Compartmentalization of GSTA4 Suppresses Ferroptosis to Drive Antiandrogen Resistance in Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Carboxypeptidase E Alleviates Depressive-Like Behaviors in Mice by Regulating BDNF/Nrf2 Axis-Mediated Ferroptosis.Neurochemical research · 2026Article
- The novel biguanide derivative 4C synergizes with talazoparib by inducing ferroptosis via the SREBP1/FASN/ SLC7A11/GPX4 axis in bladder cancer.Cell death discovery · 2026Article
- Dual regulation of metabolic reprogramming and protein competitive modifications: the core role and mechanism of MRPL36 in glioblastoma malignant progression.Journal of experimental & clinical cancer research : CR · 2026Article
- MND1 reduces breast cancer chemosensitivity by promoting RAD51-mediated homologous recombination repair.Cell death & disease · 2026Article
- USP5-C-MAF Axis Regulates Autophagy-Dependent Neuronal Ferroptosis in Spinal Cord Injury Therapeutics.CNS neuroscience & therapeutics · 2026Article
- Ferroptosis in breast cancer: From adipocyte-immune-iron regulation to therapeutic application.Clinical and translational medicine · 2026Review
- USP5 in cancer: a therapeutic window into metabolism and drug resistance.Journal of translational medicine · 2026Review
- Aberrant expression of TRIM26 suppresses ferroptosis through regulating GPX4 protein stability in colorectal cancer.Molecular biology reports · 2026Article
- The Role of Se-Containing Glutathione Peroxidases and Thioredoxin Reductases in Oncogenesis: Expression Paradoxes and Therapeutic Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- The Role of Lipid Metabolism in the Progression of Breast Cancer.Journal of Cancer · 2026Review
- S-palmitoylation of MTDH regulates ferroptosis resistance in breast cancer cell.Journal of lipid research · 2026Article
- Immune evasion driven by lipid metabolic reprogramming in endocrine-resistant HRFrontiers in immunology · 2026Review
- Protein Post-Translational Modifications in the Regulation of Ferroptosis: New Opportunities and Challenges for Cancer Immunotherapy.International journal of biological sciences · 2026Review
- Targeting glutathione peroxidase 4 in ferroptosis: from immune regulation to pharmacological development and translational applications.Frontiers in pharmacology · 2026Review
- Collagen dynamics in the breast cancer tumor microenvironment and therapeutic perspectives.Discover oncology · 2025Review
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Authors and funding
18 authors.
Funding
Abstract
Increasing studies have reported that dysregulated lipid metabolism is an independent risk factor for breast cancer (BC); it would be, therefore, enlightening to investigate the relationship between metabolic reprogramming and the tumor microenvironment in the future. Ferroptosis, a novel form of programmed cell death, is characterized by glutathione (GSH) depletion and inactivation of glutathione peroxidase 4 (GPX4), the central regulator of the antioxidant system. While the close association between fatty acid metabolism and ferroptosis has been studied in various diseases, the interplay between the key fatty acid metabolic enzyme fatty acid synthase (FASN) and ferroptosis in BC remains unexplored. At the beginning of the current study, we demonstrated that FASN expression positively correlates with an immune-cold tumor microenvironment in BC. Subsequent findings revealed that FASN knockdown promotes GPX4 degradation-induced ferroptosis, thereby enhancing the efficacy of anti-programmed cell death protein 1 (PD-1) immunotherapy. Co-immunoprecipitation coupled with mass spectrometry (IP/MS) and co-IP experiments demonstrated that ubiquitin specific protease 5 (USP5) stabilizes GPX4 by binding to and deubiquitinating it. Furthermore, knockdown of FASN inhibited the palmitoylation of USP5, reducing its interaction with GPX4 and consequently increasing GPX4 ubiquitination and degradation. Our results demonstrate that FASN suppresses ferroptosis in BC by stabilizing GPX4 via USP5-mediated mechanisms, highlighting FASN inhibition as a potential therapeutic approach to enhance immunotherapy response.
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