Table 3.
Signaling cascades commonly found in GSCs and their role within the cell. Abbreviations: Akt = v‐akt murine thymoma viral oncogene; BAX = B‐cell lymphoma 2 associated X protein; BCL‐XL = B‐cell lymphoma extra large; BCL = B‐cell lymphoma; BCL‐2 = B‐cell lymphoma 2; BMP = bone morphogenetic proteins; Bmi‐1 = B lymphoma Mo‐MLV insertion region 1 homolog; BMPR = bone morphogenetic protein receptor; CDK4 = cyclin‐dependant kinase 4; c‐Myc = myelocytomatosis; CSL = citrate synthase‐like; EGFR = epidermal growth factor receptor; Fra = fos related antigen; GSC = glioblastoma stem cell; Hes = hairy and enhancer of split 1; Hey = Hairy/enhancer‐of‐split related with YRPW; IGFBP‐2 = insulin‐like growth factor‐binding protein‐2; IGF = insulin‐like growth factor; MCL‐1 = myeloid cell leukemia‐1; PDGF‐β = platelet derived growth factor‐beta; NMDA = N‐Methyl‐D‐aspartic acid; NPC = neural precursor cell; NSC = neural stem cell; Rtk = receptor tyrosine kinase; IRS1 = insulin receptor substrate 1; WNT = Wingless‐type MMTV integration site family
| Signaling pathway | Receptor(s) | Target gene(s) | Overall role of signaling pathway | Reference |
|---|---|---|---|---|
| Notch signaling | 300 kDa single‐pass short‐range transmembrane receptor | Converted CSL becomes activator of transcription for Hes and Hey families, cyclin D and c‐myc | Essential for the maintenance and fate determination in somatic stem and progenitor cells by promoting self‐renewal and repressing differentiation | 17, 78, 93, 123, 130, 139, 156 |
| Stat3 | Ciliary neurotrophic factor family cytokine receptor | BCL‐2 family including BCL‐2, BCL‐X, BAX and MLC‐1 | Controls major cellular responses, including cell proliferation and survival. Also, the JAK‐STAT3 signaling pathway plays an essential role in the maintenance of NPCs by fibroblast growth factor 2. | 21, 31, 54, 125 |
| Rtk‐Akt | Receptor tyrosine kinases | EGFR | Activation of EGFR promotes the growth of both astrocyte precursors and neural stem cells. | 3, 95, 144 |
| Transforming growth factor beta | Serine/threonine kinase complex membrane receptor | PDGF‐β | Oncogenic stimulus in glioblastoma growth through induction of angiogenesis, immune evasion and invasion | 20, 118, 173 |
| Hedgehog‐gli signaling | Surface membrane receptor patched | Gli‐1, Cyclin D, Cyclin E, IRS1 | Regulates the behavior of stem cells particularly clonogenicity, survival, tumorigenicity and proliferation | 29, 37, 72, 88, 106, 132, 137, 175 |
| BMP | BMPR1A; BMPR1B; BMPR2 | Activin response element | Mediate a wide range of biological responses in NSCs including proliferation, differentiation and apoptosis. Instructive role in stem cell niche which favors the acquisition of the astroglial fate. BMP4 may inhibit GSCs by decreasing symmetric cell cycles that generate two GSCs on division, trigger differentiation or block proliferation | 5, 98, 115, 120 |
| Rac1‐Pak | NMDA | Cyclin D1 | Maintenance of stemness and malignant properties of glioma stem‐like cells | 83, 158, 178 |
| Wnt‐β‐catenin | Low‐density lipoprotein receptor related protein 5, 6, 10; Frizzle receptor | Wnt 1, 5a, 10b, 13; Fra‐1; c‐Myc; Cyclin D1 | Induces neuronal differentiation of neural precursor cells and promotes proliferation. It is also an important regulator of stem cell self‐renewal. | 63, 71, 79, 84, 90 |
| IGFBP‐2 | IGF‐receptor | Cyclin D1, CDK4, Cyclin E, Bmi‐1, | GSC promoting factor and a broad regulator of GSC resistance to lethal stress induced by genotoxic agents or small molecule inhibitors. Stimulates the migration of stem cells | 10, 73 |