SOX10 mediates glioblastoma cell-state plasticity
Ka-Hou Man1,2, Yonghe Wu3,4, Zhenjiang Gao3
1Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
EMBO Reports
|September 16, 2024
Summary
Glioblastoma therapy fails due to phenotypic plasticity. Suppressing SOX10 drives aggressive, stem-cell-like states, offering new therapeutic targets for this brain tumor.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Developmental Biology
Background:
- Phenotypic plasticity in glioblastoma contributes to therapeutic resistance.
- SOX10, an oligodendrocyte-lineage regulator, was previously shown to suppress glioblastoma progression.
Purpose of the Study:
- To investigate SOX10-mediated phenotypic plasticity in glioblastoma.
- To exploit this plasticity for novel glioblastoma therapy design.
Main Methods:
- Analysis of SOX10 expression in glioblastoma models.
- Single-cell transcriptome profiling of SOX10-knockdown (KD) tumors.
- Investigating the role of the Notch pathway.
- Evaluating combination therapies in mouse models.
Main Results:
- Low SOX10 expression correlates with neural stem-cell (NSC)-like glioblastoma states, induced by temozolomide treatment.
- SOX10 suppression promotes aggressive, NSC/developmental-like phenotypes, including a quiescent NSC population.
- Temozolomide and SOX10-KD induce a quiescent NSC state, which is reduced by Notch pathway inhibition.
Conclusions:
- SOX10 suppression drives glioblastoma progression via a transition to NSC/developmental cell states.
- A targetable quiescent NSC state is induced by SOX10 suppression.
- Combination therapies targeting Notch, HDAC, and PI3K pathways show therapeutic promise.
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