Inositol treatment inhibits medulloblastoma through suppression of epigenetic-driven metabolic adaptation.
作者： Maria Victoria Niklison-Chirou , Maria Victoria Niklison-Chirou , Sebastian Brandner , Steven C Clifford , M Albert Basson
DOI: 10.1038/S41467-021-22379-7
关键词: Cisplatin 、 PI3K/AKT/mTOR pathway 、 Epigenetics 、 Chromatin 、 Inositol 、 Biology 、 Medulloblastoma 、 Pathogenesis 、 Cancer research 、 Signal transduction
摘要: Deregulation of chromatin modifiers plays an essential role in the pathogenesis medulloblastoma, most common paediatric malignant brain tumour. Here, we identify a BMI1-dependent sensitivity to deregulation inositol metabolism proportion medulloblastoma. We demonstrate mTOR pathway activation and metabolic adaptation specifically medulloblastoma molecular subgroup G4 characterised by BMI1High;CHD7Low signature show this can be counteracted IP6 treatment. Finally, that synergises with cisplatin enhance its cytotoxicity vitro extends survival pre-clinical xenograft model.
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