Abstract
The most malignant brain tumor glioblastoma multiforme (GBM) is characterized by exponential growth and diffuse invasiveness. These characteristics are attributed to the varieties of common genetic lesions in genes encoding signaling proteins. These DNA damages lead to either activating mutations (Ras, PI3K, and Akt) or loss of function of tumor suppressor proteins (TP53, Rb, and PTEN). The signaling pathways induced by the altered signaling proteins play a role in the maintenance of the GBM malignant phenotype. Recent studies have elucidated various genetic alterations and critical signaling pathways involved in GBM. This has improved our understanding of GBM cell proliferation, migration, and invasion. Additionally, new exciting areas of research, such as stem cell biology and “-omics” analyses, have been recently employed for GBM studies. Many efforts are now directed to identification of signaling molecules involved in gliomagenesis and glioma stem cell maintenance. Signaling pathway analysis has resulted in novel GBM subclassifications that could integrate with conventional histopathological features providing information regarding the molecular mechanism of pathogenicity. The identification of aberrant signal transduction pathways and their role in glioma development and progression may contribute to the development of novel therapeutic targets. This chapter provides an overview of the current understanding of GBM oncogenomics, signaling pathways, and glioma stem cell signaling as well as the molecular circuitry regulating several key cellular processes.
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Abbreviations
- ALK:
-
Activin receptor-like kinase
- bFGF:
-
Basic fibroblast growth factor
- BMP:
-
Bone marrow protein
- ECM:
-
Extracellular matrix
- EGFR:
-
Epidermal growth factor receptor
- ERK:
-
Extracellular signal-regulated kinase
- Frz:
-
Frizzled receptor
- GBM:
-
Glioblastoma multiforme
- Gli:
-
Gliotactin
- GSC:
-
Glioma stem cells
- HB-EGF:
-
Heparin-binding EGF-like growth factor
- IDH1:
-
Isocitrate dehydrogenase-1
- IL-2:
-
Interleukin-2
- iPS:
-
Induced pluripotent
- JNK:
-
c-Jun N-terminal kinase
- LIF:
-
Leukemia inhibitory factor
- LIFR:
-
LIF receptor
- MAPK:
-
Mitogen-activated protein kinase (ERK1 and ERK2)
- MAPKK:
-
MAPK kinase
- MMP:
-
Matrix metalloproteinase
- NICD:
-
Intracellular domain of the Notch receptor
- NSC:
-
Neural stem cell
- PDGFRA:
-
Platelet-derived growth factor receptor A
- PDK1:
-
Phosphoinositide-dependent kinase-1
- PI3K:
-
Phosphatidylinositide-3-kinase
- PIP3:
-
Phosphatidylinositol 3,4,5-trisphosphate
- Ptch:
-
Patched homolog
- PTEN:
-
Phosphatase and tensin homolog
- RTK:
-
Receptor tyrosine kinase
- Shh:
-
Sonic hedgehog
- Smo:
-
Smoothened homolog
- Sox2:
-
Sry-related HMG-Box factor 2
- TCGA:
-
The Cancer Genome Atlas
- TGF:
-
Transforming growth factor
- TMZ:
-
Temozolomide
- TNF-α:
-
Tumor necrosis factor-α
- VEGFR:
-
Vascular endothelial cell growth factor receptor
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Nakada, M., Kita, D., Furuta, T., Watanabe, T., Hayashi, Y., Hamada, JI. (2014). Signaling Cascades Driving the Malignant Phenotype of Glioma Cells. In: Sedo, A., Mentlein, R. (eds) Glioma Cell Biology. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1431-5_3
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