ArticleProceedings of the National Academy of Sciences of the United States of America2025
FAO-fueled OXPHOS and NRF2-mediated stress resilience in MICs drive lymph node metastasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Review
- Mechanisms of fatty acid metabolism in tumor metastasis and targeted therapeutic strategies.Discover oncology · 2026Review
- Esophageal cancer: from pathogenesis to precision therapies.Signal transduction and targeted therapy · 2026Review
- Mediation of sphingolipid metabolism on the relationship between human nitrosamines exposure and esophageal cancer risk.Scientific reports · 2026Article
- Metabolic networks in the tumor microenvironment: roles of amino acid and lipid metabolism pathways in cancer progression and therapy.Experimental & molecular medicine · 2026Review
- Metabolic gene expression-based stratification and prognostic risk predictive model of head and neck squamous cell carcinoma.NPJ systems biology and applications · 2026Article
- The Lymphatic-Bone Axis in Cancer Metastasis.Cancers · 2026Review
- Mitophagy and Ubiquitination Coordinate Context-Specific Mitochondrial Quality Control and EMT/MET Plasticity to Drive Cancer Cell Invasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Single-cell omics in tumor lymph node metastasis: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Lymphatic Metastasis of Esophageal Squamous Cell Carcinoma: The Role of NRF2 and Therapeutic Strategies.Cancers · 2025Review
- FAO-fueled OXPHOS and NRF2-mediated stress resilience in MICs drive lymph node metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mitochondrial dynamics in cisplatin resistance: molecular mechanisms and therapeutic targeting.Frontiers in oncology · 2025Review
- Metabolic plasticity drives specific mechanisms of chemotherapy and targeted therapy resistance in metastatic colorectal cancer.Exploration of targeted anti-tumor therapy · 2025Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Metastasis is an inefficient process requiring cancer cells to adapt metabolically for survival and colonization in new environments. The contributions of tumor metabolic reprogramming to lymph node (LN) metastasis and its underlying mechanisms remain elusive. Through single-cell RNA sequencing, we identified rare metastasis-initiating cells (MICs) with stem-like properties that drive early LN metastasis. Integrated transcriptome, lipidomic, metabolomic, and functional analyses demonstrated that MICs depend on oxidative phosphorylation (OXPHOS) fueled by fatty acid oxidation (FAO) in the lipid-rich LN microenvironment. Mechanistically, the NRF2-SLC7A11 axis promotes glutathione synthesis to mitigate oxidative stress, thereby enhancing stress resistance and metastatic potential of MICs. Inhibition of NRF2-SLC7A11 reduced LN metastasis and sensitized tumors to cisplatin. Clinically, elevated NRF2-SLC7A11 expression was observed in tumors, with high expression correlating with LN metastasis, chemoresistance, and poor prognosis in esophageal squamous cell carcinoma (ESCC). These findings highlight the pivotal roles of FAO-fueled OXPHOS and NRF2 in LN metastasis and suggest targeting these pathways as a promising therapeutic strategy for metastatic ESCC.
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