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Inositol treatment inhibits medulloblastoma through suppression of epigenetic-driven metabolic adaptation

Author

Listed:
  • Sara Badodi

    (Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • Nicola Pomella

    (Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • Xinyu Zhang

    (Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • Gabriel Rosser

    (Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • John Whittingham

    (Centre for Craniofacial and Regenerative Biology, King’s College London)

  • Maria Victoria Niklison-Chirou

    (Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London
    University of Bath)

  • Yau Mun Lim

    (UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust)

  • Sebastian Brandner

    (UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust)

  • Gillian Morrison

    (The University of Edinburgh)

  • Steven M. Pollard

    (The University of Edinburgh)

  • Christopher D. Bennett

    (Institute of Cancer and Genomic Sciences, University of Birmingham
    Birmingham Women and Children’s Hospital)

  • Steven C. Clifford

    (Newcastle University Centre for Cancer, Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute)

  • Andrew Peet

    (Institute of Cancer and Genomic Sciences, University of Birmingham
    Birmingham Women and Children’s Hospital)

  • M. Albert Basson

    (Centre for Craniofacial and Regenerative Biology, King’s College London
    MRC Centre for Neurodevelopmental Disorders, King’s College London)

  • Silvia Marino

    (Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

Abstract

Deregulation of chromatin modifiers plays an essential role in the pathogenesis of medulloblastoma, the most common paediatric malignant brain tumour. Here, we identify a BMI1-dependent sensitivity to deregulation of inositol metabolism in a proportion of medulloblastoma. We demonstrate mTOR pathway activation and metabolic adaptation specifically in medulloblastoma of the molecular subgroup G4 characterised by a BMI1High;CHD7Low signature and show this can be counteracted by IP6 treatment. Finally, we demonstrate that IP6 synergises with cisplatin to enhance its cytotoxicity in vitro and extends survival in a pre-clinical BMI1High;CHD7Low xenograft model.

Suggested Citation

  • Sara Badodi & Nicola Pomella & Xinyu Zhang & Gabriel Rosser & John Whittingham & Maria Victoria Niklison-Chirou & Yau Mun Lim & Sebastian Brandner & Gillian Morrison & Steven M. Pollard & Christopher , 2021. "Inositol treatment inhibits medulloblastoma through suppression of epigenetic-driven metabolic adaptation," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22379-7
    DOI: 10.1038/s41467-021-22379-7
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