Notch Signaling in Glioblastoma Stem Cell Dynamics

Notch signalling is an evolutionarily conserved pathway that regulates cell fate decisions through direct cell–cell contacts. In the healthy central nervous system, it orchestrates neural stem cell maintenance, lineage commitment and differentiation. In glioblastoma, hyperactivation of Notch receptors sustains a subpopulation of glioblastoma stem cells (GSCs) characterised by self-renewal, multipotency and resistance to conventional therapies. Aberrant Notch activity drives transcriptional programmes that inhibit differentiation, promote invasion and enhance survival under hypoxia or nutrient stress. It also interfaces with key oncogenic cascades such as PI3K–AKT, NF-κB and metabolic regulators, contributing to intratumour heterogeneity. Moreover, Notch modulates the tumour microenvironment by influencing angiogenesis, immune evasion and extracellular matrix remodelling. Targeting Notch via γ-secretase inhibitors, blocking antibodies or modulation of processing enzymes offers a promising avenue to diminish the GSC pool, reverse resistance mechanisms and improve clinical outcomes.

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Notch Signaling in Glioblastoma Stem Cell Dynamics publication trend

The graph below shows the total number of articles in notch signaling in glioblastoma stem cell dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Notch Signalling: A conserved cell–cell communication pathway involving four transmembrane receptors (Notch1–4) that, upon ligand binding and proteolytic cleavage, release an intracellular domain to regulate gene transcription.

Glioblastoma Stem Cells (GSCs): A subset of tumour cells with stem-like properties, capable of self-renewal, differentiation and driving tumour recurrence and treatment resistance.

γ-Secretase Inhibitor (GSI): A compound that prevents the final proteolytic step of Notch receptor activation, thereby blocking downstream signalling.

Furin: A proprotein convertase responsible for an essential proteolytic cleavage of Notch in the trans-Golgi network, enabling receptor maturation.

Tumour Microenvironment (TME): The complex ecosystem of stromal cells, immune cells, extracellular matrix and soluble factors that surrounds and interacts with tumour cells.

References

1. G9a promotes immune suppression by targeting the Fbxw7/Notch pathway in glioma stem cells. CNS Neuroscience & Therapeutics (2023).
2. Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy. Biomolecules (2024).
3. Targeting the Notch-Furin axis with 2-hydroxyoleic acid: a key mechanism in glioblastoma therapy. Cellular Oncology (2024).