Table 1.
Summary of Ephs and Ephrins expression, functional role and localization in gliomas.
| Ephs/ Ephrins | Expression / Survival | Ligand-Dependent Effect | Downstream Signaling After Ligand-dependent Stimulation | Localization Within the Tumor | Reference |
|---|---|---|---|---|---|
| EphA2 | ↑ / ↓ | ↓ Migration and proliferation. | ↓ The MAPK pathway and blocks Akt activation. | Tumor cells, vasculature and stem cells. | (43, 45, 59, 106, 113, 122) |
| EphA3 | ↑ / ↓ | ↓ Proliferation. | ↓ The MAPK pathway. | Tumor cells, vasculature, stem cells and stroma. | (89, 156) |
| EphA4 | ↑ / - | ↑ Migration and proliferation if FGF stimulated. | ↑ The MAPK pathway and phosphorylates Akt. | Tumor cells. | (117) |
| EphA5 | ↓ / ↑ | No significant decrease in cell proliferation. | - | Plasma and platelets. | (61) |
| EphA7 | ↑ / ↓ | - | - | Tumor microvasculature. | (60) |
| ephrin-A1 | ↓ / - | Down-regulates EphA2. | - | Very low levels on tumor cells. | (45) |
| ephrin-A5 | ↓ / - | Down-regulates EphA2 and EphA3. | ↓ EGFR | Very low levels on tumor cells. | (45, 118) |
| EphB1 | ↓ / ↑ | ↓ Migration and invasion. | ↑ ERK1/2 * | - | (70) |
| EphB2 | ↑ / - | ↑ Invasion. | ↓ The MAPK and the PI3K–Akt– mTOR pathways. | Tumor vasculature. | (76–78) |
| EphB3 | ↑ / - | - | - | Tumor cells. | (70) |
| EphB4 | ↑ / ↓ | - | Pro-angiogenic effect. | Tumor cells. | (69, 98) |
| ephrin-B1 | ↑ / - | ↑ Invasion. | - | - | (68) |
| ephrin-B2 | ↑ / ↓ | ↑ Migration and invasion. | Induce VEGFR2 internalization and the downstream pathways and vessel sprouting. | - | (68, 69, 98) |
| ephrin-B3 | ↑ / - | ↑ Invasion. | - | - | (68) |
Abbreviations: ↑= Increased; ↓= Decreased; - = No data; * = not shown in gliomas; MAPK= mitogen-activated protein kinase; PI3K= phosphatidylinositol-4,5-bisphosphate 3-kinase; EGFR= epidermal growth factor receptor; mTOR= mammalian target of rapamycin; ERK= extracellular signal-regulated kinases; VEGFR2= vascular endothelial growth factor receptor-2.