ArticleCell metabolism2015
MYC Disrupts the Circadian Clock and Metabolism in Cancer Cells.
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Article in Cell metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers.
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182citing papers in PubMed
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182 citing papers in PubMed, 271 citations in OpenAlex.
- Advances in monitoring mammalian circadian components and their rhythms using reporter systems.RSC chemical biology · 2026Review
- Modulation of the tumor microenvironment through BMAL1-LHX8 axis augments the sensitivity of ameloblastoma to vemurafenib.Journal of advanced research · 2026Article
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Transient MYC Mimicking the Exercise Response Orchestrates Multifaceted Skeletal Muscle Adaptations.bioRxiv : the preprint server for biology · 2026Article
- c-MYC is Transcribed in a Circadian Manner and Acts a Clock Disruptor whose Timing Minimizes its Impacts.bioRxiv : the preprint server for biology · 2026Article
- Circadian clock control of breast cancer hallmarks: molecular mechanisms and therapeutic implications.Cancer metastasis reviews · 2026Review
- Molecular mechanisms of circadian clock-mediated gene regulation and their implications in leukemia.Molecular biology reports · 2026Review
- Interplay between circadian and other transcription factors-Implications for cycling transcriptome reprogramming.FEBS letters · 2026Review
- Rhythms of risk: the intersection of clocks, cancer, and chronotherapy.The Journal of clinical investigation · 2026Review
- The circadian clock regulates scavenging of fluid-borne substrates by brain border-associated macrophages.bioRxiv : the preprint server for biology · 2025Article
- Targeting the hepatic circadian clock concomitant with tyrosine kinase inhibition reverses late-stage hepatocellular carcinoma.Cell reports · 2025Article
- Promoter Frame Position Affects Strength and Nature of Circadian Oscillations inInternational journal of molecular sciences · 2025Article
- The multifaceted impact of circadian disruption on cancer risk: a systematic review of insights and economic implications.Journal of the National Cancer Center · 2025Review
- Haoya Wang Et Al.: Circadian Rhythm Disruption Promotes Tumor Progression Through Upregulated Glycolysis.Cancer medicine · 2025Review
- Spatiotemporal Heterogeneity of Tumor Glucose Metabolism Reprogramming: From Single-Cell Mechanisms to Precision Interventions.International journal of molecular sciences · 2025Review
- Inhibiting the REV-ERBα expression protects against mechanical overloading-induced cartilage clock disruption and osteoarthritis progression.Journal of orthopaedic translation · 2025Article
- Evaluation of the Circadian Rhythm Component Cipc (Clock-Interacting Pacemaker) in Leukemogenesis: A Literature Review and Bioinformatics Approach.Clocks & sleep · 2025Review
- The diverse roles of the circadian clock in cancer.Nature cancer · 2025Review
- Rhythm is essential: Unraveling the relation between the circadian clock and cancer.Critical reviews in oncology/hematology · 2025Review
- Article
122 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 7 institutions in 1 country.
Brian J AltmanAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Annie L HsiehAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Arjun SenguptaDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Saikumari Y KrishnanaiahDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Zachary E StineAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Zandra E WaltonAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Arvin M GouwAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Anand VenkataramanDepartment of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Bo LiAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Pankuri Goraksha-HicksDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Sharon J DiskinAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
David I BellovinDivision of Medical Oncology, Departments of Medicine and Pathology, Stanford School of Medicine, Stanford, CA 94304, USA.
M Celeste SimonAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jeffrey C RathmellDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA; Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA; Department of Immunology, Duke University, Durham, NC 27710, USA.
Mitchell A LazarDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
John M MarisAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Dean W FelsherDivision of Medical Oncology, Departments of Medicine and Pathology, Stanford School of Medicine, Stanford, CA 94304, USA.
John B HogeneschDepartment of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Aalim M WeljieDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Chi V DangAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: dangvchi@exchange.upenn.edu.
Cancer Research Institute · USTranslational Therapeutics (United States) · USChildren's Hospital of Philadelphia · USDuke University · USStanford Medicine · USJohns Hopkins University · USUniversity of Pennsylvania · US
Funding
UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3MTranslational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Rebecca A Simmons · 2006 to 2026
$35.3MTRANSLATIONAL CONTROL IN ADAPTATION TO HYPOXIAP01CA104838 · NCI · UNIVERSITY OF PENNSYLVANIA · PI DIEHL, JOHN ALAN · 2004 to 2018
$17.6MREV-ERB Nuclear Receptors in Circadian Rhythm and MetabolismR01DK045586 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL A. LAZAR · 1992 to 2026
$12.0MC-MYC TARGETS IN THE PATHOGENESIS OF HUMAN CANCERSR01CA057341 · NCI · WISTAR INSTITUTE · PI DANG, CHI V. · 1992 to 2021
$8.3MMolecular, Cellular and Physiological Mechanisms of the Mammalian Circadian ClockR01NS054794 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI HOGENESCH, JOHN B, LIU, ANDREW C. · 2007 to 2022
$8.1MMYC--TRANSCRIPTION AND INTERACTION WITH P107R01CA051497 · NCI · WISTAR INSTITUTE · PI DANG, CHI V. · 1995 to 2025
$5.3MGlucose metabolism and cell death in cancerR01CA123350 · NCI · DUKE UNIVERSITY · PI RATHMELL, JEFFREY C. · 2007 to 2011
$1.5MIdentifying Strategies to Increase Engagement in Clinical Trials in Pediatric SCDRC1MD004418 · NIMHD · CHILDREN'S HOSP OF PHILADELPHIA · PI BARAKAT, LAMIA P · 2009 to 2010
$813kUnderstanding Glutaminase Alternative Splicing in Cancer MetabolismF32CA174148 · NCI · UNIVERSITY OF PENNSYLVANIA · PI STINE, ZACHARY E · 2013 to 2015
$159kOncogenic Disruption of Circadian Rhythm and ChronotherapyF32CA180370 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ALTMAN, BRIAN JAMES · 2014 to 2015
$113kDisruption of circadian rhythm in hypoxiaF30CA200347 · NCI · UNIVERSITY OF PENNSYLVANIA · PI WALTON, ZANDRA ELENE · 2015 to 2016
$78kNCI NIH HHS F30 CA200347NCI NIH HHS F30CA200347NCI NIH HHS F32 CA174148NCI NIH HHS F32CA174148NCI NIH HHS F32 CA180370NCI NIH HHS F32CA180370NCI NIH HHS P01 CA104838NCI NIH HHS P30 CA016520NCI NIH HHS R01 CA051497NCI NIH HHS R01 CA057341NCI NIH HHS R01CA057341NCI NIH HHS R01 CA123350NIDDK NIH HHS R01 DK045586NIEHS NIH HHS P30 ES013508NIMHD NIH HHS RC1 MD004418NIMHD NIH HHS RC1MD004418NINDS NIH HHS R01 NS054794
Abstract
The MYC oncogene encodes MYC, a transcription factor that binds the genome through sites termed E-boxes (5'-CACGTG-3'), which are identical to the binding sites of the heterodimeric CLOCK-BMAL1 master circadian transcription factor. Hence, we hypothesized that ectopic MYC expression perturbs the clock by deregulating E-box-driven components of the circadian network in cancer cells. We report here that deregulated expression of MYC or N-MYC disrupts the molecular clock in vitro by directly inducing REV-ERBα to dampen expression and oscillation of BMAL1, and this could be rescued by knockdown of REV-ERB. REV-ERBα expression predicts poor clinical outcome for N-MYC-driven human neuroblastomas that have diminished BMAL1 expression, and re-expression of ectopic BMAL1 in neuroblastoma cell lines suppresses their clonogenicity. Further, ectopic MYC profoundly alters oscillation of glucose metabolism and perturbs glutaminolysis. Our results demonstrate an unsuspected link between oncogenic transformation and circadian and metabolic dysrhythmia, which we surmise to be advantageous for cancer.
Indexed as
ARNTL Transcription FactorsBase SequenceBinding SitesCell Line, TumorCircadian RhythmCLOCK ProteinsDimerizationGenes, ReporterGlucoseGlutamineHumansNuclear Receptor Subfamily 1, Group D, Member 1Period Circadian ProteinsPromoter Regions, GeneticProto-Oncogene Proteins c-mycReceptors, Cytoplasmic and NuclearARNTL Transcription FactorsCLOCK ProteinsGlucoseGlutamineNR1D1 protein, humanNR1D2 protein, humanNuclear Receptor Subfamily 1, Group D, Member 1PER2 protein, humanPeriod Circadian ProteinsProto-Oncogene Proteins c-mycReceptors, Cytoplasmic and NuclearRepressor ProteinsRNA, MessengerRNA, Small Interfering
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