ArticleCell metabolism2018
Translational and HIF-1α-Dependent Metabolic Reprogramming Underpin Metabolic Plasticity and Responses to Kinase Inhibitors and Biguanides.
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Article in Cell metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48citing papers in PubMed
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48 citing papers in PubMed, 86 citations in OpenAlex.
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- Exploiting metabolic adaptations to overcome dabrafenib treatment resistance in melanoma cells.Molecular oncology · 2026Article
- Spatiotemporal control of mitoribosome-mediated metabolic reprogramming in cancer: implications for heterogeneity and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- NMR metabolomics in genetically engineered mouse models.Biophysical reviews · 2025Review
- New mesenchymal stem/stromal cell-based strategies for osteoarthritis treatment: targeting macrophage-mediated inflammation to restore joint homeostasis.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosis.iScience · 2025Article
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- PPARγ-dependent remodeling of translational machinery in adipose progenitors is impaired in obesity.Cell reports · 2024Article
- ING5 inhibits aerobic glycolysis of lung cancer cells by promoting TIE1-mediated phosphorylation of pyruvate dehydrogenase kinase 1 at Y163.Frontiers of medicine · 2024Article
- The crosstalk between metabolism and translation.Cell metabolism · 2024Review
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- Immunosurveillance encounters cancer metabolism.EMBO reports · 2024Review
- Compensatory cross-talk between autophagy and glycolysis regulates senescence and stemness in heterogeneous glioblastoma tumor subpopulations.Acta neuropathologica communications · 2023Article
- PI3K/AKT/mTOR Dysregulation and Reprogramming Metabolic Pathways in Renal Cancer: Crosstalk with the VHL/HIF Axis.International journal of molecular sciences · 2023Review
- Metabolic targeting of malignant tumors: a need for systemic approach.Journal of cancer research and clinical oncology · 2023Review
- Mitotic CDK1 and 4E-BP1 II: A single phosphomimetic mutation in 4E-BP1 induces glucose intolerance in mice.PloS one · 2023Article
- EIF4A inhibition targets bioenergetic homeostasis in AML MOLM-14 cells in vitro and in vivo and synergizes with cytarabine and venetoclax.Journal of experimental & clinical cancer research : CR · 2022Article
- Review
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Authors and funding
28 authors at 9 institutions in 5 countries.
Laura HuleaLady Davis Institute, SMBD JGH, McGill University, Montreal, QC H3A 1A3, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H3A 1A3, Canada.
Simon-Pierre GravelGoodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, QC, Canada.
Masahiro MoritaDepartment of Molecular Medicine and Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Institute of Resource Developmental and Analysis, Kumamoto University, Kumamoto 860-8111, Japan.
Marie CargnelloLady Davis Institute, SMBD JGH, McGill University, Montreal, QC H3A 1A3, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H3A 1A3, Canada; Centre de Recherche en Cancérologie de Toulouse, 31100 Toulouse, France.
Oro UchenunuLady Davis Institute, SMBD JGH, McGill University, Montreal, QC H3A 1A3, Canada; Department of Experimental Medicine, McGill University, Montreal, QC H3A 1A3, Canada.
Young Kyuen ImLady Davis Institute, SMBD JGH, McGill University, Montreal, QC H3A 1A3, Canada; Department of Experimental Medicine, McGill University, Montreal, QC H3A 1A3, Canada.
Camille LehuédéGoodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Experimental Medicine, McGill University, Montreal, QC H3A 1A3, Canada.
Eric H MaGoodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3A 1A3, Canada.
Matthew LeibovitchLady Davis Institute, SMBD JGH, McGill University, Montreal, QC H3A 1A3, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H3A 1A3, Canada.
Shannon McLaughlanLady Davis Institute, SMBD JGH, McGill University, Montreal, QC H3A 1A3, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H3A 1A3, Canada.
Marie-José BlouinLady Davis Institute, SMBD JGH, McGill University, Montreal, QC H3A 1A3, Canada.
Maxime ParisottoDépartement de Chimie, Université de Montréal, Montréal, QC H3C 3J7, Canada.
Vasilios PapavasiliouGoodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
Cynthia LavoieGoodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
Ola LarssonDepartment of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, 171 16 Stockholm, Sweden.
Michael OhhDepartment of Laboratory Medicine and Pathobiology and Department of Biochemistry, University of Toronto, Toronto, ON M5S1A8, Canada.
Tiago FerreiraMcGill University Centre for Research in Neuroscience, Montreal General Hospital, Montreal, QC H3G 1A4, Canada.
Celia GreenwoodLady Davis Institute, SMBD JGH, McGill University, Montreal, QC H3A 1A3, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC H3A 1A3, Canada; Department of Human Genetics, McGill University, Montreal, QC H3A 1A3, Canada.
Gaëlle BridonGoodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
Daina AvizonisGoodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
Gerardo FerbeyreDépartement de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal, QC H3C 3J7, Canada.
Peter SiegelGoodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada.
Russell G JonesGoodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3A 1A3, Canada.
William MullerGoodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Department of Experimental Medicine, McGill University, Montreal, QC H3A 1A3, Canada.
Josie Ursini-SiegelLady Davis Institute, SMBD JGH, McGill University, Montreal, QC H3A 1A3, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H3A 1A3, Canada; Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Department of Experimental Medicine, McGill University, Montreal, QC H3A 1A3, Canada.
Julie St-PierreGoodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, Microbiology, and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Michael PollakLady Davis Institute, SMBD JGH, McGill University, Montreal, QC H3A 1A3, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H3A 1A3, Canada; Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Experimental Medicine, McGill University, Montreal, QC H3A 1A3, Canada. Electronic address: michael.pollak@mcgill.ca.
Ivan TopisirovicLady Davis Institute, SMBD JGH, McGill University, Montreal, QC H3A 1A3, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Department of Experimental Medicine, McGill University, Montreal, QC H3A 1A3, Canada. Electronic address: ivan.topisirovic@mcgill.ca.
McGill University Health Centre · CAMcGill University · CAUniversité de Montréal · CACentre de Recherche en Cancérologie de Toulouse · FRMontreal General Hospital · CAScience for Life Laboratory · SEThe University of Texas Health Science Center at San Antonio · USUniversity of Ottawa · CAUniversity of Toronto · CA
Funding
Control of Protein Synthesis by the UPS Under StressR01CA202021 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI RONAI, ZEEV A. · 2016 to 2020
$2.3MCIHR FDN-148373CIHR MOP-111143CIHR MOP-363027NCI NIH HHS R01 CA202021
Abstract
There is increasing interest in therapeutically exploiting metabolic differences between normal and cancer cells. We show that kinase inhibitors (KIs) and biguanides synergistically and selectively target a variety of cancer cells. Synthesis of non-essential amino acids (NEAAs) aspartate, asparagine, and serine, as well as glutamine metabolism, are major determinants of the efficacy of KI/biguanide combinations. The mTORC1/4E-BP axis regulates aspartate, asparagine, and serine synthesis by modulating mRNA translation, while ablation of 4E-BP1/2 substantially decreases sensitivity of breast cancer and melanoma cells to KI/biguanide combinations. Efficacy of the KI/biguanide combinations is also determined by HIF-1α-dependent perturbations in glutamine metabolism, which were observed in VHL-deficient renal cancer cells. This suggests that cancer cells display metabolic plasticity by engaging non-redundant adaptive mechanisms, which allows them to survive therapeutic insults that target cancer metabolism.
Indexed as
Drug Resistance, NeoplasmNeoplasmsAdaptor Proteins, Signal TransducingAmino AcidsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBiguanidesCell Cycle ProteinsEukaryotic Initiation FactorsGene Expression Regulation, NeoplasticHCT116 CellsHumansHypoxia-Inducible Factor 1, alpha SubunitK562 CellsMechanistic Target of Rapamycin Complex 1MiceAdaptor Proteins, Signal TransducingAmino AcidsBiguanidesCell Cycle ProteinsEIF4EBP1 protein, humanEIF4EBP2 protein, humanEukaryotic Initiation FactorsHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitMechanistic Target of Rapamycin Complex 1PhosphoproteinsProtein Kinase InhibitorsRNA, MessengerbiguanidecancerHIF-1αkinase inhibitormetabolic plasticitymetabolismmRNA translationmTORC1non-essential amino acids
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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.