Role of Notch Signaling Pathway in Glioblastoma Pathogenesis

Notch signaling is an evolutionarily conserved pathway that regulates important biological processes, such as cell proliferation, apoptosis, migration, self-renewal, and differentiation. In mammals, Notch signaling is composed of four receptors (Notch1⁻4) and five ligands (Dll1-3⁻4, Jagged1⁻2) that...

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Bibliographic Details
Published in:Cancers 2019-03, Vol.11 (3), p.292
Main Authors: Bazzoni, Riccardo, Bentivegna, Angela
Format: Article
Language:English
Subjects:
Apoptosis
Brain cancer
Brain tumors
Cell cycle
Cell differentiation
Cell migration
Cell proliferation
Cell self-renewal
Central nervous system
Cyclin-dependent kinases
Epidermal growth factor
Glioblastoma
Glioma cells
Homeostasis
Jagged1 protein
Kinases
Ligands
Mutation
Neural stem cells
Neurogenesis
Neurons
Notch1 protein
Pathogenesis
Phenotypes
Proteins
Review
Signal transduction
Stem cells
Tumor cells
Tumorigenesis
Tumors
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Summary:Notch signaling is an evolutionarily conserved pathway that regulates important biological processes, such as cell proliferation, apoptosis, migration, self-renewal, and differentiation. In mammals, Notch signaling is composed of four receptors (Notch1⁻4) and five ligands (Dll1-3⁻4, Jagged1⁻2) that mainly contribute to the development and maintenance of the central nervous system (CNS). Neural stem cells (NSCs) are the starting point for neurogenesis and other neurological functions, representing an essential aspect for the homeostasis of the CNS. Therefore, genetic and functional alterations to NSCs can lead to the development of brain tumors, including glioblastoma multiforme (GBM). GBM remains an incurable disease, and the reason for the failure of current therapies and tumor relapse is the presence of a small subpopulation of tumor cells known as glioma stem cells (GSCs), characterized by their stem cell-like properties and aggressive phenotype. Growing evidence reveals that Notch signaling is highly active in GSCs, where it suppresses differentiation and maintains stem-like properties, contributing to GBM tumorigenesis and conventional-treatment resistance. In this review, we try to give a comprehensive view of the contribution of Notch signaling to GBM and its possible implication as a target for new therapeutic approaches.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers11030292