RRC ID 81501
Author Diaz LR, Gil-Ranedo J, Jaworek KJ, Nsek N, Marques JP, Costa E, Hilton DA, Bieluczyk H, Warrington O, Hanemann CO, Futschik ME, Bossing T, Barros CS.
Title Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth.
Journal EMBO Rep
Abstract Cell commitment to tumourigenesis and the onset of uncontrolled growth are critical determinants in cancer development but the early events directing tumour initiating cell (TIC) fate remain unclear. We reveal a single-cell transcriptome profile of brain TICs transitioning into tumour growth using the brain tumour (brat) neural stem cell-based Drosophila model. Prominent changes in metabolic and proteostasis-associated processes including ribogenesis are identified. Increased ribogenesis is a known cell adaptation in established tumours. Here we propose that brain TICs boost ribogenesis prior to tumour growth. In brat-deficient TICs, we show that this dramatic change is mediated by upregulated HEAT-Repeat Containing 1 (HEATR1) to promote ribosomal RNA generation, TIC enlargement and onset of overgrowth. High HEATR1 expression correlates with poor glioma patient survival and patient-derived glioblastoma stem cells rely on HEATR1 for enhanced ribogenesis and tumourigenic potential. Finally, we show that HEATR1 binds the master growth regulator MYC, promotes its nucleolar localisation and appears required for MYC-driven ribogenesis, suggesting a mechanism co-opted in ribogenesis reprogramming during early brain TIC development.
Volume 25(1)
Pages 168-197
Published 2024-1-1
DOI 10.1038/s44319-023-00017-1
PII 10.1038/s44319-023-00017-1
PMID 38225354
PMC PMC10897169
MeSH Animals Brain / metabolism Brain Neoplasms* / metabolism Carcinogenesis / pathology Cell Transformation, Neoplastic / pathology DNA-Binding Proteins / metabolism Drosophila / genetics Drosophila / metabolism Drosophila Proteins / genetics Drosophila Proteins / metabolism Glioblastoma* / metabolism Glioma / pathology Humans Minor Histocompatibility Antigens* / metabolism Neoplastic Stem Cells / metabolism Proto-Oncogene Proteins c-myc* / metabolism RNA-Binding Proteins* / metabolism
Resource
Drosophila DGRC#114346