ArticleCell death & disease2023
FSP1 confers ferroptosis resistance in KEAP1 mutant non-small cell lung carcinoma in NRF2-dependent and -independent manner.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 47 citations in OpenAlex.
- Translating the Crosstalk Between Unfolded Protein Response and Ferroptosis to Cancer Therapies.Current oncology reports · 2026Review
- NRF2 activation is required for chemotherapy resistance acquisition in medulloblastoma via metabolic and redox adaptation.Redox biology · 2026Article
- P53 Competitively Binds P300 to Suppress HIF-1α/TFRC-Mediated Ferroptosis and Promote Doxorubicin Resistance in Breast Cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Sal-hDPSCs Transplantation Alleviates Hypoxic-Ischaemic Ferroptosis in Neonatal Rats Via the FSP1-CoQInternational dental journal · 2026Article
- Opposing roles of DGAT-mediated lipid droplet biogenesis in the regulation of ferroptosis sensitivity.The FEBS journal · 2026Article
- Intrinsic polyunsaturated fatty acid synthesis capacity dictates ferroptosis sensitivity under restricted arachidonic acid availability.Cell death discovery · 2026Article
- Ferroptosis Resistance: Redundant Antioxidant Networks Are a Barrier to Cancer Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- TCM-Derived Small Molecules Targeting Metabolic Vulnerabilities in NSCLC: Ferroptosis-Centered Mechanisms and Emerging Cuproptosis- and Disulfidptosis-Related Vulnerabilities.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Ferroptosis-induced oxidative stress in therapy-resistant glioblastoma.Cell death discovery · 2026Article
- Molecular mechanisms of FSP1-regulated ferroptosis and therapeutic implications in various cancers.Cellular & molecular biology letters · 2026Review
- The biphasic interactions between ferroptosis and oxidative stress: from molecular mechanisms to disease interventions.Molecular biology reports · 2026Review
- The Dual Role of Ferroptosis in Cancer: Molecular Mechanisms, Microenvironment Crosstalk, and Precision Therapeutics.Cancers · 2026Review
- Programmed cell death in lung cancer: mechanisms, immune responses, and therapeutics.Apoptosis : an international journal on programmed cell death · 2026Review
- Decoding the spatiotemporal characteristics of ferroptosis: reshaping tumour therapeutic strategies.Experimental hematology & oncology · 2026Review
- Methionine metabolism is linked with phospholipid and glutamine metabolism to drive ferroptosis.Cell reports · 2026Article
- Targeting ferroptosis in cancer: from mechanistic insights to therapeutic approaches.Molecular biomedicine · 2026Review
- Pirin Transcriptionally Regulates PLA2G4A To Inhibit Ferroptosis in Colorectal Cancer via Lipid Profile Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epigenetic and post-translational regulatory networks of ferroptosis in the tumor immune microenvironment.Experimental hematology & oncology · 2026Review
- Metabolic control of ferroptosis in cancer: lipid dependencies as therapeutic vulnerabilities.Frontiers in oncology · 2026Review
- Nanozyme-Driven Ferroptosis-Cuproptosis Interplay in Lung Cancer.International journal of nanomedicine · 2026Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis, a type of cell death induced by lipid peroxidation, has emerged as a novel anti-cancer strategy. Cancer cells frequently acquire resistance to ferroptosis. However, the underlying mechanisms are poorly understood. To address this issue, we conducted a thorough investigation of the genomic and transcriptomic data derived from hundreds of human cancer cell lines and primary tissue samples, with a particular focus on non-small cell lung carcinoma (NSCLC). It was observed that mutations in Kelch-like ECH-associated protein 1 (KEAP1) and subsequent nuclear factor erythroid 2-related factor 2 (NRF2, also known as NFE2L2) activation are strongly associated with ferroptosis resistance in NSCLC. Additionally, AIFM2 gene, which encodes ferroptosis suppressor protein 1 (FSP1), was identified as the gene most significantly correlated with ferroptosis resistance, followed by multiple NRF2 targets. We found that inhibition of NRF2 alone was not sufficient to reduce FSP1 protein levels and promote ferroptosis, whereas FSP1 inhibition effectively sensitized KEAP1-mutant NSCLC cells to ferroptosis. Furthermore, we found that combined inhibition of FSP1 and NRF2 induced ferroptosis more intensely. Our findings imply that FSP1 is a crucial suppressor of ferroptosis whose expression is partially dependent on NRF2 and that synergistically targeting both FSP1 and NRF2 may be a promising strategy for overcoming ferroptosis resistance in cancer.
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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.