Primary GSCs have high Notch-2 expression. Constitutive Notch-2 signaling in neural stem cells generates similar features to GSCs. Notch signaling represents a pathway common in the midst of regulating the GSC phenotype.
Often amplified and mutated in high-grade gliomas. Increases proliferation and tumorigenicity, inhibits apoptosis, regulates angiogenesis and stemness, and mediates resistance to oxidative stress and ionizing radiation.
Reduce proliferation and abolish tumorigenicity. Induce differentiation, determined by an increase in the number of glial fibrillary acidic protein- (GFAP-) positive cells and delay tumor growth.
In GSCs, Hedgehog-Gli signaling increases expression of stem genes (e.g., CD133, Olig2, Oct4, Nanog, and Sox2), promotes self-renewal, and supports glioma growth and survival. Proliferation of NSC and GSC. Activation of SHH pathway in brainstem glioma.
Transcription factors and chromatin-modifying proteins
Bmi1 (polycomb complex protein)
Found in undifferentiated NSCs and high grade gliomas, with higher expression correlating to poor glioma patient survival. Found enriched in GSCs and required for their self-renewal.
Oct4 is highly expressed in human gliomas and correlates with tumor grade, promotes colony formation, and inhibits differentiation in glioma cells, potentially through upregulation of phosphorylated STAT3.
Nanog expression is higher in GSCs, coexpressed with CD133+ glioma cells and less expressed in regions enriched for the differentiation marker, GFAP. Interacts with the Hedgehog-Gli pathway to modulate GSC proliferation, neurosphere formation, and tumor promotion in orthotopic xenografts.
c-Myc levels correlate with glioma tumor grade and are highly expressed in GSCs relative to non-GSCs. Not only does c-Myc promote proliferation, but it may also represent a GSC-specific survival factor. c-Myc is highly expressed in approximately half of CD133+ cells acutely isolated from primary human GBM specimens, whereas c-Myc expression is considerably lower in the CD133− fraction.
Highly expressed in diffuse gliomas including astrocytomas, oligodendrogliomas, and oligoastrocytomas. Controls GSC proliferation, cell adhesion, and cell cycle progression.
Protein alteration favors tumorigenesis. NSC and HSC display Musashi alteration. Consistently correlated with the tumor proliferation in gliomas. Expressed in GSCs and in neurospheres derived from brain tumors, being correlated with tumor grade and proliferation rate.
Frequently expressed in high grade gliomas, especially in primary tumors in patients with dissemination, being a predictive marker for poor survival rate. Positive coexpression for Nestin/CD133 is an indicator of poor prognosis.