ORCID
- C. Oliver Hanemann: 0000-0002-1951-1025
- Matthias E. Futschik: 0000-0002-6245-8071
- Torsten Bossing: 0000-0002-3277-9130
- Claudia S. Barros: 0000-0003-0361-0333
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.
DOI
10.1038/s44319-023-00017-1
Publication Date
2024-01-12
Publication Title
EMBO Reports
Volume
25
Issue
1
ISSN
1469-221X
Keywords
Brain Tumourigenesis, HEATR1, MYC, Neural Stem Cells, Ribogenesis
First Page
168
Last Page
197
Recommended Citation
Barros, C., Diaz, L., Gil-Ranedo, J., Jaworek, K., Nsek, N., Marques, J., Costa, E., Hilton, D., Bieluczyk, H., Warrington, O., Hanemann, C., Futschik, M., & Bossing, T. (2024) 'Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth', EMBO Reports, 25(1), pp. 168-197. Available at: https://doi.org/10.1038/s44319-023-00017-1
