ArticleMolecular cell2018
The PLAG1-GDH1 Axis Promotes Anoikis Resistance and Tumor Metastasis through CamKK2-AMPK Signaling in LKB1-Deficient Lung Cancer.
Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 213 papers.
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213 citing papers in PubMed, 338 citations in OpenAlex.
- Alterations to the Bronchial Gene-Expression Effects of Tobacco Smoking in People Living With HIV.Journal of acquired immune deficiency syndromes (1999) · 2026Trial
- An Anoikis-Related Gene Signature Associated With Stromal Remodeling and Clinical Outcome in Gastric Cancer.Chemical biology & drug design · 2026Article
- Review
- FOXA2 enhances anoikis sensitivity in lung adenocarcinoma cells: Dual role of ABCA8 upregulation and NOX4 suppression.Oncology letters · 2026Article
- α-KG conformationally stabilizes nuclear GLUD1-SNAIL complex to fuel trans-endothelial migration in metastasis.Nature communications · 2026Article
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- Nanoparticle-based strategies targeting disulfidptosis, anoikis, and PANoptosis for enhanced cancer therapy.Journal of nanobiotechnology · 2026Review
- IDH2 lactylation regulates mitochondrial dysfunction injury induced by myocardial ischemia‑reperfusion via the AMPK signaling pathway.International journal of molecular medicine · 2026Article
- Detachment-Induced FAK-STAT3-NNMT Inhibits CTCs Anoikis to Promote Breast Cancer Metastasis by Enhancing Fatty Acid Oxidation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Establishment and validation of a novel anoikis-related prognostic signature of lung squamous cell carcinoma.Translational cancer research · 2026Article
- Review
- Anoikis-Related Genes Signature Contributes to Predicting Prognosis and Response to Immunotherapy in Lung Squamous Cell Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2026Article
- AKT1 phosphorylates PRMT7 to promote GLUD1 methylation and gastric cancer progression.Cell death & disease · 2026Article
- ATP2C2-PLA2R1 axis underlies lipid metabolism modulation and invasion in papillary thyroid carcinoma mediated by a VGIC signature.Discover oncology · 2026Article
- GLUD1 supports ovarian cancer progression by counteracting anoikis via ARAF/MEK/ERK signaling.NPJ precision oncology · 2026Article
- X-Linked Inhibitor of Apoptosis Protein (XIAP) Contributes to ERK1/2-Mediated Anoikis Resistance in Hepatocellular Carcinoma.MedComm - Oncology · 2026Article
- α-Ketoglutarate dictates AMPK protein synthesis for energy sensing in human cancers.Nature chemical biology · 2026Article
- Prognostic prediction and immune correlation analysis of anoikis- and epithelial-mesenchymal transition-related genes in lung adenocarcinoma.Translational cancer research · 2026Article
- PDHA1 enhances resistance to ferroptosis in anoikis-resistant prostate cancer by upregulating AIFM2.Cell death discovery · 2026Article
- Oblique-incidence reflectivity difference technology identifies the antiviral drug Ribavirin as an inhibitor of lung tumor progression by targeting AMPK signaling.Journal of pharmaceutical analysis · 2026Article
153 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Loss of LKB1 is associated with increased metastasis and poor prognosis in lung cancer, but the development of targeted agents is in its infancy. Here we report that a glutaminolytic enzyme, glutamate dehydrogenase 1 (GDH1), upregulated upon detachment via pleomorphic adenoma gene 1 (PLAG1), provides anti-anoikis and pro-metastatic signals in LKB1-deficient lung cancer. Mechanistically, the GDH1 product α-KG activates CamKK2 by enhancing its substrate AMPK binding, which contributes to energy production that confers anoikis resistance. The effect of GDH1 on AMPK is evident in LKB1-deficient lung cancer, where AMPK activation predominantly depends on CamKK2. Targeting GDH1 with R162 attenuated tumor metastasis in patient-derived xenograft model and correlation studies in lung cancer patients further validated the clinical relevance of our finding. Our study provides insight into the molecular mechanism by which GDH1-mediated metabolic reprogramming of glutaminolysis mediates lung cancer metastasis and offers a therapeutic strategy for patients with LKB1-deficient lung cancer.
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