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Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth
Laura R Diaz1, Jon Gil-Ranedo1, Karolina J Jaworek1,2
1Peninsula Medical School, Faculty of Health, John Bull Building, University of Plymouth, PL6 8BU, Plymouth, UK.
EMBO Reports
|January 15, 2024
Summary
Brain tumor-initiating cells (TICs) boost ribogenesis before tumor growth, driven by HEATR1. High HEATR1 expression in gliomas correlates with poor survival, highlighting its role in cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Developmental Biology
Background:
- Tumorigenesis involves cell fate decisions and uncontrolled growth, but early events directing tumor-initiating cell (TIC) fate are unclear.
- Ribogenesis, the process of ribosome biogenesis, is a known adaptation in established tumors.
Purpose of the Study:
- To investigate the early events and molecular mechanisms driving brain TIC fate and tumor initiation.
- To explore the role of ribogenesis in pre-tumorigenic brain TICs.
Main Methods:
- Single-cell transcriptome profiling of brain TICs in a Drosophila neural stem cell-based model.
- Analysis of HEAT-Repeat Containing 1 (HEATR1) expression and function in TICs.
- Correlation analysis with glioma patient survival data and patient-derived glioblastoma stem cells.
- Investigation of HEATR1 interaction with MYC.
Main Results:
- Brain TICs exhibit prominent changes in metabolic processes, including enhanced ribogenesis, prior to tumor growth.
- Upregulated HEATR1 promotes ribosomal RNA generation, TIC enlargement, and overgrowth in brat-deficient TICs.
- High HEATR1 expression correlates with poor glioma patient survival.
- Patient-derived glioblastoma stem cells depend on HEATR1 for enhanced ribogenesis and tumor potential.
- HEATR1 binds MYC, promotes its nucleolar localization, and is required for MYC-driven ribogenesis.
Conclusions:
- Brain TICs upregulate ribogenesis via HEATR1 before tumor growth, representing an early cancer development mechanism.
- HEATR1 is a critical driver of early brain TIC development and a potential biomarker for glioma prognosis.
- HEATR1-MYC interaction offers a mechanistic insight into ribogenesis reprogramming during early brain TIC development.
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