ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2014
LKB1 Loss induces characteristic patterns of gene expression in human tumors associated with NRF2 activation and attenuation of PI3K-AKT.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Pooled it
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- Clinical efficacy of atezolizumab plus bevacizumab and chemotherapy inJournal for immunotherapy of cancer · 2022Trial
- Tumor-Derived Complement C3 Overexpression in STK11-Mutant Lung Adenocarcinoma Drives Tumor Growth and Immune Checkpoint Inhibitor Resistance.Cancer immunology research · 2026Article
- Targeting CRTC2 reversesProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Tumor suppressor genes and KRAS G12C inhibitor resistance in non-small cell lung cancer.iScience · 2026Review
- Transcriptional reprogramming triggered by neonatal UV radiation or Lkb1 loss prevents BRAFOncogene · 2025Article
- Impact of Co-mutations and Transcriptional Signatures in Non-Small Cell Lung Cancer Patients Treated with Adagrasib in the KRYSTAL-1 Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Review
- Metabolic reprogramming and therapeutic targeting in non-small cell lung cancer: emerging insights beyond the Warburg effect.Frontiers in oncology · 2025Review
- Article
- Article
- Impact of LKB1 status on radiation outcome in patients with stage III non-small-cell lung cancer.Scientific reports · 2024Article
- A community challenge to predict clinical outcomes after immune checkpoint blockade in non-small cell lung cancer.Journal of translational medicine · 2024Article
- Tissue- and liquid-biopsy based NGS profiling in advanced non-small-cell lung cancer in a real-world setting: the IMMINENT study.Frontiers in oncology · 2024Article
- Molecular markers of metastatic disease in KRAS-mutant lung adenocarcinoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2023Article
- HDAC3 is critical in tumor development and therapeutic resistance inScience advances · 2023Article
- CDK4/6 inhibition triggers ICAM1-driven immune response and sensitizes LKB1 mutant lung cancer to immunotherapy.Nature communications · 2023Article
- LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer.Nature communications · 2022Article
- Loss of LKB1-NUAK1 signalling enhances NF-κB activity in a spheroid model of high-grade serous ovarian cancer.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
introductionInactivation of serine/threonine kinase 11 (STK11 or LKB1) is common in lung cancer, and understanding the pathways and phenotypes altered as a consequence will aid the development of targeted therapeutic strategies. Gene and protein expressions in a murine model of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (Kras)-mutant lung cancer have been studied to gain insight into the biology of these tumors. However, the molecular consequences of LKB1 loss in human lung cancer have not been fully characterized.
methodsWe studied gene expression profiles associated with LKB1 loss in resected lung adenocarcinomas, non-small-cell lung cancer cell lines, and murine tumors. The biological significance of dysregulated genes was interpreted using gene set enrichment and transcription factor analyses and also by integration with somatic mutations and proteomic data.
resultsLoss of LKB1 is associated with consistent gene expression changes in resected human lung cancers and cell lines that differ substantially from the mouse model. Our analysis implicates novel biological features associated with LKB1 loss, including altered mitochondrial metabolism, activation of the nuclear respiratory factor 2 (NRF2) transcription factor by kelch-like ECH-associated protein 1 (KEAP1) mutations, and attenuation of the phosphatidylinositiol 3-kinase and v-akt murine thymoma viral oncogene homolog (PI3K/AKT) pathway. Furthermore, we derived a 16-gene classifier that accurately predicts LKB1 mutations and loss by nonmutational mechanisms. In vitro, transduction of LKB1 into LKB1-mutant cell lines results in attenuation of this signature.
conclusionLoss of LKB1 defines a subset of lung adenocarcinomas associated with characteristic molecular phenotypes and distinctive gene expression features. Studying these effects may improve our understanding of the biology of these tumors and lead to the identification of targeted treatment strategies.
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