ArticleCell death and differentiation2025
Lactate dehydrogenase B noncanonically promotes ferroptosis defense in KRAS-driven lung cancer.
Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- LDH isozymes as targets for cancer therapy.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Ferroptosis: Newly Emerged Regulator for Human Disease.MedComm · 2026Review
- CCDC137 affects sorafenib resistance in hepatocellular carcinoma cells by activating the AKT/mTOR signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Dynamic changes in liver-to-spleen ratio: can it be a prognostic biomarker for chemo-immunotherapy in small cell lung cancer?Translational lung cancer research · 2026Article
- The dual role of the crosstalk between autophagy and ferroptosis in lung cancer treatment: Advances in mechanisms and therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- The controversial role of metabolic reprogramming in anti-tumor therapy resistance.Discover oncology · 2026Review
- Lactate Dehydrogenase B delactylation promotes gastric cancer metastasis via enhancing glutathione-mediated resistance to ferroptosis.Cell biology and toxicology · 2026Article
- Oxysophoridine promotes osteoarthritis repair via GSH system activation and ROS suppression.Scientific reports · 2026Article
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Dual role of lactate in ferroptosis: Mechanisms, pathophysiology and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- ppAT drives glutamine-dependent purine biosynthesis and malignant progression in hepatocellular carcinoma.BMC cancer · 2026Article
- [Research Progress on Glycolytic Reprogramming and Lactylation Crosstalk in Tumors].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Immunometabolic control of macrophage plasticity in wound healing: mechanistic insights and therapeutic opportunities.Frontiers in immunology · 2026Review
- GBP2 condensates promote ferroptosis to sensitize anti-PD-L1 immunotherapy in melanoma.Nature communications · 2025Article
- Machine learning identifies lactate metabolism biomarkers and deciphers immune infiltration landscapes in Parkinson's disease.Scientific reports · 2025Article
- Lactate and lactylation: molecular insights into histone and non-histone lactylation in tumor progression, tumor immune microenvironment, and therapeutic strategies.Biomarker research · 2025Review
- The integration of transcriptomics and metabolomics elucidates the antitumor mechanisms of mycophenolic acid in bladder cancer cells.BMC cancer · 2025Article
- Recharacterization of the Tumor Suppressive Mechanism of RSL3 Identifies the Selenoproteome as a Druggable Pathway in Colorectal Cancer.Cancer research · 2025Article
- Ubiquinol-mediated suppression of mitochondria-associated ferroptosis is a targetable function of lactate dehydrogenase B in cancer.Nature communications · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Ferroptosis is an oxidative, non-apoptotic cell death frequently inactivated in cancer, but the underlying mechanisms in oncogene-specific tumors remain poorly understood. Here, we discover that lactate dehydrogenase (LDH) B, but not the closely related LDHA, subunits of active LDH with a known function in glycolysis, noncanonically promotes ferroptosis defense in KRAS-driven lung cancer. Using murine models and human-derived tumor cell lines, we show that LDHB silencing impairs glutathione (GSH) levels and sensitizes cancer cells to blockade of either GSH biosynthesis or utilization by unleashing KRAS-specific, ferroptosis-catalyzed metabolic synthetic lethality, culminating in increased glutamine metabolism, oxidative phosphorylation (OXPHOS) and mitochondrial reactive oxygen species (mitoROS). We further show that LDHB suppression upregulates STAT1, a negative regulator of SLC7A11, thereby reducing SLC7A11-dependent GSH metabolism. Our study uncovers a previously undefined mechanism of ferroptosis resistance involving LDH isoenzymes and provides a novel rationale for exploiting oncogene-specific ferroptosis susceptibility to treat KRAS-driven lung cancer.
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