ArticleCancer discovery2018
Cross-Cohort Analysis Identifies a TEAD4-MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma.
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Article in Cancer discovery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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106citing papers in PubMed
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106 citing papers in PubMed.
- Article
- Developmental and MAPK-responsive transcription factors regulate distinct malignant cell states and associated genetic dependencies in pancreatic cancer.Nature genetics · 2026Article
- The Hippo signaling pathway in pediatric brain tumors: molecular mechanisms and therapeutic opportunities.Cancer metastasis reviews · 2026Review
- Systematic design of combination therapy by targeting master regulators of coexisting diffuse midline glioma cell states.Nature genetics · 2026Article
- Comprehensive transcriptomics and proteome analysis to identify prognostic risk factors for MYCN non-amplified high-risk neuroblastoma.Human genomics · 2026Article
- Degradation of the TEAD•YAP/TAZ Transcription Factor Complex by Heterobifunctional Small Molecules that Bind to the TEAD Allosteric Lipid Pocket.bioRxiv : the preprint server for biology · 2026Article
- Article
- Synergistic inhibition of CHK1 and MUS81 to combat replication stress resistance in high-risk neuroblastoma.Scientific reports · 2025Article
- Review
- Novel Strategy for Acquiring Metabolically-Tagged Nascent Extracellular Vesicles: Implications for Identifying Surface Protein Markers of Extracellular Vesicles From Neuroblastoma Cells Cultured With Native Serum.Journal of extracellular vesicles · 2025Article
- Restoring mitochondrial quantity and quality to reverse the Warburg effect and drive neuroblastoma differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- DKC1-mediated pseudouridylation of rRNA targets hnRNP A1 to sustain IRES-dependent translation and ATF4-driven metabolic adaptation.Science advances · 2025Article
- Arginine depletion potentiates standard-of-care chemo-immunotherapy in preclinical models of high-risk neuroblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Disruption of the KLHL37-N-Myc complex restores N-Myc degradation and arrests neuroblastoma growth in mouse models.The Journal of clinical investigation · 2025Article
- Apoptosis-inducing factor (AIF) at the crossroad of cell survival and cell death: implications for cancer and mitochondrial diseases.Cell communication and signaling : CCS · 2025Review
- Identification and targeting of regulators of SARS-CoV-2-host interactions in the airway epithelium.Science advances · 2025Article
- Prognostic role and tumor-suppressive effects of CADM family members and the potential molecular mechanisms of CADM1 in neuroblastoma.Discover oncology · 2025Article
- The regulatory architecture of the primed pluripotent cell state.Nature communications · 2025Article
- A feedback loop between Paxillin and Yorkie sustains Drosophila intestinal homeostasis and regeneration.Nature communications · 2025Article
- Cell types or cell states? An investigation of adrenergic and mesenchymal cell phenotypes in neuroblastoma.iScience · 2024Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors.
Presha Rajbhandari *Department of Systems Biology, Columbia University, New York, New York.
Gonzalo Lopez *Department of Systems Biology, Columbia University, New York, New York.
Claudia CapdevilaDepartment of Systems Biology, Columbia University, New York, New York.
Beatrice SalvatoriDepartment of Systems Biology, Columbia University, New York, New York.
Jiyang YuDepartment of Systems Biology, Columbia University, New York, New York.
Ruth Rodriguez-BarruecoDepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
Daniel MartinezDivision of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Mark YarmarkovichDivision of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Nina Weichert-LeaheyDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Brian J AbrahamWhitehead Institute for Biomedical Research, Cambridge, Massachusetts.
Mariano J AlvarezDepartment of Systems Biology, Columbia University, New York, New York.
Archana IyerDepartment of Systems Biology, Columbia University, New York, New York.
Jo Lynne HarenzaDivision of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Derek OldridgeDivision of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Katleen De PreterCenter for Medical Genetics & Cancer Research Institute Ghent (CRIG), Ghent University, Gent, Belgium.
Jan KosterDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Shahab AsgharzadehDivision of Hematology/Oncology, Saban Research Institute, The Children's Hospital Los Angeles, Los Angeles, California.
Robert C SeegerDivision of Hematology/Oncology, Saban Research Institute, The Children's Hospital Los Angeles, Los Angeles, California.
Jun S WeiGenetics Branch, Oncogenomics Section, Center for Cancer Research, NIH, Bethesda, Maryland.
Javed KhanGenetics Branch, Oncogenomics Section, Center for Cancer Research, NIH, Bethesda, Maryland.
Jo VandesompeleCenter for Medical Genetics & Cancer Research Institute Ghent (CRIG), Ghent University, Gent, Belgium.
Pieter MestdaghCenter for Medical Genetics & Cancer Research Institute Ghent (CRIG), Ghent University, Gent, Belgium.
Rogier VersteegDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
A Thomas LookDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Richard A YoungWhitehead Institute for Biomedical Research, Cambridge, Massachusetts.
Antonio IavaroneDepartment of Neurology and Pathology and Cell Biology, Institute for Cancer Genetics, Columbia University, New York, New York.
Anna LasorellaDepartment of Pediatrics and Pathology and Cell Biology, Institute for Cancer Genetics, Columbia University, New York, New York.
Jose M SilvaDepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
John M MarisDivision of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. ac2248@cumc.columbia.edu maris@chop.edu.
Andrea CalifanoDepartment of Systems Biology, Columbia University, New York, New York. ac2248@cumc.columbia.edu maris@chop.edu.
Funding
COG FOREIGN ACCRUALU10CA098543 · NCI · NATIONAL CHILDHOOD CANCER FOUNDATION · PI ADAMSON, PETER C. · 2003 to 2013
$335.5MCOG SDMC - Statistics CoreU10CA180899 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TODD A ALONZO · 2014 to 2026
$132.8MTumor microenvironment-dependent therapy resistanceP01CA217959 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI Kimberly Stegmaier · 2017 to 2026
$20.7MPredicting Cancer Cell Response to Endogenous and Exogenous Perturbations at the Single Cell LevelR35CA197745 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2015 to 2026
$11.5MSystematic pharmacological targeting of the core mechanisms responsible for maintaining cancer cell stateU54CA209997 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA, HONIG, BARRY H · 2016 to 2021
$10.9MBIOINFORMATICS: SYSTEMS BIOLOGY OF PEDIATRIC CANCERSZIABC011002 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KHAN, JAVED · 2009 to 2025
$9.3MDiscovering mechanisms of neuroblastoma tumorigenesis to improve patient outcomesR35CA220500 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI JOHN M MARIS · 2017 to 2026
$8.7MSystems Biology of Tumor Progression and Drug ResistanceU01CA168426 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2012 to 2016
$6.5MCELLULAR AND MOLECULAR FOUNDATIONS OF BIOMEDICAL SCIENCET32GM008798 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI PRYWES, RON M · 2001 to 2018
$6.3MSystematic Identification and Pharmacological Targeting of Tumor Dependencies for Precision Cancer MedicineU01CA217858 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2017 to 2021
$6.1MRole of LMO1 in Neuroblastoma Initiation and MaintenanceR01CA180692 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI LOOK, A. THOMAS, MARIS, JOHN M · 2015 to 2019
$3.0MHigh-performance compute cluster for biomedical computingS10OD012351 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2012 to 2012
$2.0MNCI NIH HHS P01 CA217959NCI NIH HHS R01 CA180692NCI NIH HHS R35 CA197745NCI NIH HHS R35 CA220500NCI NIH HHS U01 CA168426NCI NIH HHS U01 CA217858NCI NIH HHS U10 CA098543NCI NIH HHS U10 CA180899NCI NIH HHS U54 CA209997NIGMS NIH HHS T32 GM008798NIH HHS S10 OD012351NIH HHS S10 OD021764
Abstract
High-risk neuroblastomas show a paucity of recurrent somatic mutations at diagnosis. As a result, the molecular basis for this aggressive phenotype remains elusive. Recent progress in regulatory network analysis helped us elucidate disease-driving mechanisms downstream of genomic alterations, including recurrent chromosomal alterations. Our analysis identified three molecular subtypes of high-risk neuroblastomas, consistent with chromosomal alterations, and identified subtype-specific master regulator proteins that were conserved across independent cohorts. A 10-protein transcriptional module-centered around a TEAD4-MYCN positive feedback loop-emerged as the regulatory driver of the high-risk subtype associated with
Indexed as
Gene Expression Regulation, NeoplasticRegulatory Sequences, Nucleic AcidAcyltransferasesCell Cycle ProteinsCell Line, TumorComputational BiologyDNA-Binding ProteinsGene Expression ProfilingHumansMuscle ProteinsNeoplasm StagingNeuroblastomaN-Myc Proto-Oncogene ProteinNuclear ProteinsProteasome Endopeptidase ComplexRNA InterferenceAcyltransferasesCell Cycle ProteinsDNA-Binding ProteinsMuscle ProteinsMYCN protein, humanN-Myc Proto-Oncogene ProteinNuclear ProteinsProteasome Endopeptidase ComplexTAFAZZIN protein, humanTEAD4 protein, humanTEA Domain Transcription FactorsTranscription FactorsYY1AP1 protein, human
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