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

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 BMI1^High;CHD7^Low 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 BMI1^High;CHD7^Low xenograft model.

SUBMITTER: Badodi S

PROVIDER: S-EPMC8042111 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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

Badodi Sara S Pomella Nicola N Zhang Xinyu X Rosser Gabriel G Whittingham John J Niklison-Chirou Maria Victoria MV Lim Yau Mun YM Brandner Sebastian S Morrison Gillian G Pollard Steven M SM Bennett Christopher D CD Clifford Steven C SC Peet Andrew A Basson M Albert MA Marino Silvia S

Nature communications 20210412 1

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 BMI1<sup>High</sup>;CHD7<sup>Low</sup> signature and show this can be counteracted ...[more]

PMID: 33846320

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