ArticleCancer cell2018
The GSK3 Signaling Axis Regulates Adaptive Glutamine Metabolism in Lung Squamous Cell Carcinoma.
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Article in Cancer cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 3 of them syntheses that pooled it.
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121citing papers in PubMed, 3 pooled it
7.0field-weighted citation impact, top 2% of its field
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Who cites it
121 citing papers in PubMed, 3 syntheses or guidelines pooled it, 181 citations in OpenAlex.
- Metabolomics and metabolites in cancer diagnosis and treatment.Molecular biomedicine · 2025Pooled it
- Innovative technologies and their clinical prospects for early lung cancer screening.Clinical and experimental medicine · 2025Pooled it
- A Systematic Review of the Metabolism of High-Grade Gliomas: Current Targeted Therapies and Future Perspectives.International journal of molecular sciences · 2024Pooled it
- 70 Years of DON and Beyond: Glutaminase Inhibition as a Synergistic Strategy in Cancer Combination Therapy.Pharmaceutics · 2026Review
- Dual inhibition of glycolysis and glutaminolysis by targeting FOXO3 for hepatocellular carcinoma treatment.Oncogene · 2026Article
- Association Between CDH1 Downregulation and Lymphocyte Cell-Cycle Dysfunction in Alzheimer's Disease and Mild Cognitive Impairment.Cellular and molecular neurobiology · 2026Article
- Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.Amino acids · 2026Review
- The lncRNA DAMER selectively guides mNature cell biology · 2026Article
- Article
- Hypoxia and aspirin additively increase intracellular glutamine accumulation in PIK3CA-mutated colorectal cancer cells.Scientific reports · 2026Article
- Dual-action peptide KWHVeterinary research · 2026Article
- Macropinocytosis and Vascularization Determine Response to mTOR Inhibitors in Lung Squamous Cell Carcinoma.Cancer research · 2026Article
- Ammonia metabolic reprogramming in the tumor microenvironment: emergence of an immunosuppressive niche.Frontiers in cell and developmental biology · 2026Review
- Dual Metabolic Inhibition by Berberine and Glutor Triggers AMPK/JNK-Dependent DNA Damage in Cancer Cells.International journal of medical sciences · 2026Article
- Modeling and targeting the hostile physicochemical niche in bone metastasis: from experimental platforms to niche-directed therapy.Frontiers in cell and developmental biology · 2026Review
- Catabolic rewiring in cancer impacts dietary interventions.Communications biology · 2025Review
- Recent insights into the roles and therapeutic potentials of GLS1 in inflammatory diseases.Journal of pharmaceutical analysis · 2025Review
- Harnessing GSK-3β inhibition for lung cancer therapy: emerging opportunities and challenges.Medical oncology (Northwood, London, England) · 2025Review
- Refining treatment strategies for non-small cell lung cancer lacking actionable mutations: insights from multi-omics studies.British journal of cancer · 2025Review
- The protein phosphatase 6 subunit SAPS3 modulates lifespan by regulating metabolism.Science advances · 2025Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 4 institutions in 1 country.
Milica MomcilovicDepartment of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Sean T BaileyDepartment of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Jason T LeeDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Crump Institute for Molecular Imaging, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Michael C FishbeinDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Daniel BraasDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; UCLA Metabolomics Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
James GoDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Thomas G GraeberDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; UCLA Metabolomics Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Francesco ParlatiCalithera Biosciences, South San Francisco, CA 94080, USA.
Susan DemoCalithera Biosciences, South San Francisco, CA 94080, USA.
Rui LiDepartment of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Tonya C WalserDepartment of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Michael GricowskiMemorial Care Health System, Long Beach, CA 90806, USA.
Robert ShumanMemorial Care Health System, Long Beach, CA 90806, USA.
Julio IbarraMemorial Care Health System, Long Beach, CA 90806, USA.
Deborah FridmanHoag Memorial Hospital Presbyterian, Newport Beach, CA 92663, USA.
Michael E PhelpsDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Crump Institute for Molecular Imaging, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Karam BadranDepartment of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Maie St JohnDepartment of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Nicholas M BernthalDepartment of Orthopedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Noah FedermanJonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Jane YanagawaDepartment of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Thoracic Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Steven M DubinettDepartment of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Saman SadeghiDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Heather R ChristofkDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; UCLA Metabolomics Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
David B ShackelfordDepartment of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. Electronic address: dshackelford@mednet.ucla.edu.
University of California, Los Angeles · USMemorialCare Health System · USCalithera (United States) · USHoag Memorial Hospital Presbyterian · US
Funding
Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Melissa Fitzmaurice Neligan · 1985 to 2026
$134.5MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MTARGETED COMBINATORIAL TREATMENT OF BRAF MELANOMASP01CA168585 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DRY, SARAH M. · 2013 to 2017
$8.4MUCLA Pulmonary and Critical Care Medicine Training ProgramT32HL072752 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JOHN A BELPERIO, TOMAS GANZ · 2003 to 2026
$8.3MUCLA Clinical and Translational Science InstituteKL2TR000122 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$4.5MNCATS NIH HHS KL2 TR000122NCATS NIH HHS UL1 TR000124NCI NIH HHS P01 CA168585NCI NIH HHS P30 CA016042NHLBI NIH HHS T32 HL072752
Abstract
Altered metabolism is a hallmark of cancer growth, forming the conceptual basis for development of metabolic therapies as cancer treatments. We performed in vivo metabolic profiling and molecular analysis of lung squamous cell carcinoma (SCC) to identify metabolic nodes for therapeutic targeting. Lung SCCs adapt to chronic mTOR inhibition and suppression of glycolysis through the GSK3α/β signaling pathway, which upregulates glutaminolysis. Phospho-GSK3α/β protein levels are predictive of response to single-therapy mTOR inhibition while combinatorial treatment with the glutaminase inhibitor CB-839 effectively overcomes therapy resistance. In addition, we identified a conserved metabolic signature in a broad spectrum of hypermetabolic human tumors that may be predictive of patient outcome and response to combined metabolic therapies targeting mTOR and glutaminase.
Indexed as
AnimalsBenzeneacetamidesBoron CompoundsCarcinoma, Squamous CellCell Line, TumorCell ProliferationCell SurvivalDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticGlutamineGlycineGlycogen Synthase Kinase 3GlycolysisHumansKi-67 AntigenLung NeoplasmsBenzeneacetamidesBoron CompoundsCB-839GlutamineGlycineGlycogen Synthase Kinase 3Ki-67 AntigenMKI67 protein, humanMLN2238ThiadiazolesCB-839GLSglutaminolysisglycolysisGSK3α/βlung squamous cell carcinomametabolic signaturemTORPET imaging
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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.