ArticleCancer discovery2023
LKB1-Dependent Regulation of TPI1 Creates a Divergent Metabolic Liability between Human and Mouse Lung Adenocarcinoma.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Mapping protein states and interactions across the tree of life with co-fractionation mass spectrometry.Nature communications · 2023Pooled it
- Tumor-Derived Complement C3 Overexpression in STK11-Mutant Lung Adenocarcinoma Drives Tumor Growth and Immune Checkpoint Inhibitor Resistance.Cancer immunology research · 2026Article
- Zinc finger protein 544 promotes hepatocellular carcinoma by generating an immunosuppressive tumor microenvironment.JHEP reports : innovation in hepatology · 2026Article
- NSUN2/m5C/TPI1 axis promotes glycolysis and immune evasion in breast cancer.Journal of translational medicine · 2026Article
- Construction of chronic inflammation and mitochondrial energy metabolism-associated predictive and therapeutic models for lung adenocarcinoma patients.Discover oncology · 2026Article
- The fluoroquinoline compound exerts anti-erythroleukemic effects by dual-targeting GLUT1 and the PI3K/AKT signaling pathway.Scientific reports · 2026Article
- Post-translational modifications of triosephosphate isomerase reveal metabolic vulnerabilities in T-ALL: effect of combining dichloroacetic acid and the PPI rabeprazole.The Biochemical journal · 2026Article
- Metabolic permissiveness: how tissue context shapes cancer.Genes & development · 2026Review
- Glucose and Lactate, Starters or Intermediates of Cancer Metabolic Rewiring.Advances in experimental medicine and biology · 2026Review
- FAM189A2 activates Hippo signaling pathway by abrogating WWP2-mediated LATS1 ubiquitination, to inhibit the glycolysis and proliferation processes of lung adenocarcinoma.Journal of translational medicine · 2025Article
- SCAMP3-Driven Regulation of ERK1/2 and Autophagy Phosphoproteomics Signatures in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Article
- Targeting LKB1/STK11-mutant cancer: distinct metabolism, microenvironment, and therapeutic resistance.Trends in pharmacological sciences · 2025Review
- Article
- The roles of KRAS in cancer metabolism, tumor microenvironment and clinical therapy.Molecular cancer · 2025Review
- The role and therapeutic potential of glucose metabolism in multidrug resistance of cancer.Frontiers in cell and developmental biology · 2025Review
- Altered metabolism in cancer: insights into energy pathways and therapeutic targets.Molecular cancer · 2024Review
- Inhibition of ULK1/2 and KRASeLife · 2024Article
- Diversity of post-translational modifications and cell signaling revealed by single cell and single organelle mass spectrometry.Communications biology · 2024Article
- Genome-wide CRISPR screens in spheroid culture reveal that the tumor suppressor LKB1 inhibits growth via the PIKFYVE lipid kinase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The role of STK11/LKB1 in cancer biology: implications for ovarian tumorigenesis and progression.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
KRAS is the most frequently mutated oncogene in human lung adenocarcinomas (hLUAD), and activating mutations frequently co-occur with loss-of-function mutations in TP53 or STK11/LKB1. However, mutation of all three genes is rarely observed in hLUAD, even though engineered comutation is highly aggressive in mouse lung adenocarcinoma (mLUAD). Here, we provide a mechanistic explanation for this difference by uncovering an evolutionary divergence in the regulation of triosephosphate isomerase (TPI1). In hLUAD, TPI1 activity is regulated via phosphorylation at Ser21 by the salt inducible kinases (SIK) in an LKB1-dependent manner, modulating flux between the completion of glycolysis and production of glycerol lipids. In mice, Ser21 of TPI1 is a Cys residue that can be oxidized to alter TPI1 activity without a need for SIKs or LKB1. Our findings suggest this metabolic flexibility is critical in rapidly growing cells with KRAS and TP53 mutations, explaining why the loss of LKB1 creates a liability in these tumors. SIGNIFICANCE: Utilizing phosphoproteomics and metabolomics in genetically engineered human cell lines and genetically engineered mouse models (GEMM), we uncover an evolutionary divergence in metabolic regulation within a clinically relevant genotype of human LUAD with therapeutic implications. Our data provide a cautionary example of the limits of GEMMs as tools to study human diseases such as cancers. This article is highlighted in the In This Issue feature, p. 799.
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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.