ArticleCancer research2025
SCD1 Inhibition Blocks the AKT-NRF2-SLC7A11 Pathway to Induce Lipid Metabolism Remodeling and Ferroptosis Priming in Lung Adenocarcinoma.
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 30 papers.
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Who cites it
30 citing papers in PubMed.
- Stearoyl CoA desaturase 1 deficiency increases ferroptosis susceptibility in chicken embryonic liver cells.Poultry science · 2026Article
- The pivotal role of SCD1 in digestive cancers: Bridging lipid metabolic reprogramming and programmed cell death (Review).International journal of oncology · 2026Review
- Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- TWF1 inhibition overcomes cisplatin resistance in NSCLC by inducing ferroptosis via p53-dependent SLC7A11 repression and autophagy-mediated glutathione metabolism reprogramming.Cancer gene therapy · 2026Article
- A fungal-derived benzothiazole derivative overcomes osimertinib resistance in NSCLC by targeting SCD1.Natural products and bioprospecting · 2026Article
- Review
- Ribonucleotide Reductase Inhibition Triggers Ferroptosis in Genetically Defined Subsets of Non-Small Cell Lung Cancer.Cancer research communications · 2026Article
- LKB1 Loss Sensitizes Lung Tumor Spheres to Mitomet-Induced Ferroptosis, and These Effects are Enhanced by mTOR Inhibition.Molecular carcinogenesis · 2026Article
- Stearoyl-CoA desaturase 1 integrates tissue-specific oncogenic pathways into a pan-cancer ferroptosis resistance program.Cell death & disease · 2026Review
- Based on artificial intelligence-assisted generation and in-depth in-silico evaluation of potential inhibitors targeting Stearoyl-CoA desaturase 1 (SCD-1).Scientific reports · 2026Article
- Targeting the lipid desaturation network in cancer: from metabolic plasticity to precision therapeutics.Journal of experimental & clinical cancer research : CR · 2026Review
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- Tipping the balance: NRF2's dual role in ferroptotic fate.Oncogenesis · 2026Review
- QSOX1 confers ferroptosis resistance via redox modification of SLC7A11 in colorectal cancer.Cellular & molecular biology letters · 2026Article
- EBF3 suppresses lung adenocarcinoma progression and immune evasion via transcriptional repression of CCL24.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- From Variant to Biomarker in NSCLC Immunotherapy Resistance: Multiomics Evidence Chains and Accountable AI Integration.Human mutation · 2026Review
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
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Authors and funding
14 authors.
Funding
Abstract
Concurrent inactivating mutations in STK11 and KEAP1 drive primary resistance to therapies, leading to worse outcomes in KRAS-mutated lung adenocarcinoma (KRASmut LUAD), and are associated with metabolic alterations. Elucidation of the underlying biology of this aggressive LUAD subset is needed to develop effective treatments to improve patient outcomes. Our transcriptomic analysis of 5,498 "real-world" KRASmut LUADs demonstrated that STK11/KEAP1 co-mutation led to upregulation of fatty acid and redox signaling pathways and considerable enrichment of the metabolic genes SCD1 and SLC7A11. High expression of SCD1 and SLC7A11 predicted poor prognosis in KRASmut patients. Transcriptomics, lipidomics, and kinase arrays in preclinical models demonstrated that SCD1 inhibition promoted ferroptosis, altered fatty acid metabolism, and downregulated SLC7A11 via AKT-GSK3β-NRF2 signaling. SCD1 inhibition caused appreciable tumor regression in xenografts and augmented the efficacy of the ferroptosis inducer erastin. Overall, this study provides insights into the role of the SCD1-SLC7A11 axis in regulating metabolic programming and predicting poor patient outcomes in a genetically defined subset of KRASmut LUAD. SIGNIFICANCE: SCD1 and SLC7A11 are prognostic biomarkers and therapeutic targets for KRAS/STK11/KEAP1 co-mutant lung adenocarcinoma, which will refocus mechanistic studies and lead to treatment strategies for lung cancer.
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