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Updated: Aug 16, 2026
07:11
Maintaining Human Glioblastoma Cellular Diversity Ex vivo using Three-Dimensional Organoid Culture
Published on: August 25, 2022
H2AX phosphorylation driven by the SET-PP2A axis maintains glioma stem cell properties
Chunhua Han1, Na Li1, Ananya Banerjee1
1Department of Radiation Oncology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Genes & Diseases
|August 15, 2026
Summary
Histone variant H2AX and its phosphorylation are crucial for maintaining glioma stem cell (GSC) self-renewal and tumor growth. Targeting the SET-PP2A pathway may offer new glioblastoma therapies.
Area of Science:
- Cancer Biology
- Molecular Oncology
- Epigenetics
Background:
- Glioma stem cells (GSCs) drive glioblastoma (GBM) relapse and invasion.
- Mechanisms regulating GSC stemness and gene expression, particularly histone roles, are not fully understood.
Purpose of the Study:
- Investigate the role of histone variant H2AX in GSC maintenance.
- Elucidate the regulatory mechanisms of H2AX phosphorylation in GSCs.
- Identify potential therapeutic targets for GBM.
Main Methods:
- CRISPR-Cas9 gene editing to delete and reintroduce H2AX.
- Analysis of H2AX and phosphorylated H2AX (γH2AX) levels in GSCs.
- Investigation of the SET-PP2A pathway's role in regulating γH2AX.
Main Results:
- GSCs exhibit increased H2AX and γH2AX levels.
- H2AX deletion impairs GSC self-renewal and tumorigenicity.
- H2AX phosphorylation, not just its presence, is essential for GSC properties.
- Elevated γH2AX results from suppressed PP2A activity due to SET oncoprotein upregulation.
- PP2A reactivation reduces γH2AX levels in GSCs.
Conclusions:
- H2AX phosphorylation is a critical regulator of GSC maintenance.
- The SET-PP2A axis controls γH2AX levels in GSCs.
- This pathway represents a potential therapeutic target for disrupting GSC-driven glioblastoma growth.
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