ArticleNature metabolism2020
The hexosamine biosynthesis pathway is a targetable liability in KRAS/LKB1 mutant lung cancer.
Article in Nature metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 137 citations in OpenAlex.
- Genes, fuel, and fate in lung cancer.Biochemical Society transactions · 2026Review
- Molecular insights and therapeutic implications for the tumor suppressor role of LKB1 in non-small cell lung cancer.Cancer letters · 2026Review
- GSLR Drives Lung Adenocarcinoma as a Critical Regulator of Energy Homeostasis Through Creatine Kinase B Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Role of Esterase BmeFE4 in Mediating the Alleviating Effects of Resveratrol on NaF-Induced Fluorosis inToxics · 2026Article
- Genetic and biochemical screens identify MGAT1 as a druggable glycosyltransferase target in STK11-mutant lung cancer.The Journal of biological chemistry · 2026Article
- Stanniocalcin 1 contributes to glioma stem cells phenotypic plasticity through NOTCH1/STAT3/GFPT2 axis.Oncogenesis · 2026Article
- Glutamine stress promotes metastatic potential via hexosamine biosynthetic pathway activity in KRAS/STK11-mutant lung adenocarcinoma.Research square · 2026Article
- O-GlcNAcylation: the metabolic-immune translator in tumor evolution and treatment.Molecular medicine (Cambridge, Mass.) · 2026Review
- GFPT2 upregulation predicts poor prognosis and is associated with TGF-β/Smad activation in lung adenocarcinoma.Discover oncology · 2026Article
- Progress of metabolomics-centric multi-omics research in medicine.iMetaOmics · 2026Review
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Hyperglycosylation is a metabolic driver of Alzheimer's disease.Nature metabolism · 2026Article
- Decoding the Hexosamine Biosynthesis Pathway: Implications for Novel Therapeutic Strategies in Sarcoma.Journal of cellular physiology · 2026Review
- Stress adaptation pathways and HA-CD44 signaling maintain the survival of pancreatic cancer cells with centrosome amplification.Cell communication and signaling : CCS · 2026Article
- GFAT2-mediated HSPD1 O-GlcNAcylation drives chemotherapy resistance in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Targeting UAP1 with rabeprazole: a novel repurposed therapeutic strategy for multiple myeloma.Frontiers in pharmacology · 2026Article
- Metabolic adaptations in cancer progression.Physiological reviews · 2026Review
- FOXO1 links KRAS G12D and G12V alleles to glutamine and nitrogen metabolism in colorectal cancer.EMBO reports · 2026Article
- Glutamine: fructose-6-phosphate amidotransferase (GFAT) in the pathology of diseases: a review.Cell death discovery · 2025Review
- Myosin-actin pattern links matrix stiffness to GFAT2-hyaluronan metabolism.Materials today. Bio · 2025Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 2 countries.
Funding
Abstract
In non-small-cell lung cancer (NSCLC), concurrent mutations in the oncogene KRAS and the tumour suppressor STK11 (also known as LKB1) encoding the kinase LKB1 result in aggressive tumours prone to metastasis but with liabilities arising from reprogrammed metabolism. We previously demonstrated perturbed nitrogen metabolism and addiction to an unconventional pathway of pyrimidine synthesis in KRAS/LKB1 co-mutant cancer cells. To gain broader insight into metabolic reprogramming in NSCLC, we analysed tumour metabolomes in a series of genetically engineered mouse models with oncogenic KRAS combined with mutations in LKB1 or p53. Metabolomics and gene expression profiling pointed towards activation of the hexosamine biosynthesis pathway (HBP), another nitrogen-related metabolic pathway, in both mouse and human KRAS/LKB1 co-mutant tumours. KRAS/LKB1 co-mutant cells contain high levels of HBP metabolites, higher flux through the HBP pathway and elevated dependence on the HBP enzyme glutamine-fructose-6-phosphate transaminase [isomerizing] 2 (GFPT2). GFPT2 inhibition selectively reduced KRAS/LKB1 co-mutant tumour cell growth in culture, xenografts and genetically modified mice. Our results define a new metabolic vulnerability in KRAS/LKB1 co-mutant tumours and provide a rationale for targeting GFPT2 in this aggressive NSCLC subtype.
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