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Cancers 2019, 11(3), 292; https://doi.org/10.3390/cancers11030292

Role of Notch Signaling Pathway in Glioblastoma Pathogenesis

1
Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Pz.le Scuro 10, 37134 Verona, Italy
2
Program in Clinical and Experimental Biomedical Sciences, University of Verona, 37134 Verona, Italy
3
NeuroMi, Milan Center for Neuroscience, Department of Neurology and Neuroscience, San Gerardo Hospital, University of Milano-Bicocca, 20900 Monza, Italy
4
School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, Italy
*
Author to whom correspondence should be addressed.
Received: 30 December 2018 / Revised: 17 February 2019 / Accepted: 25 February 2019 / Published: 1 March 2019
(This article belongs to the Special Issue Glioblastoma: State of the Art and Future Perspectives)
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Abstract

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. Glioblastoma 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 Glioblastoma tumorigenesis and conventional-treatment resistance. In this review, we try to give a comprehensive view of the contribution of Notch signaling to Glioblastoma and its possible implication as a target for new therapeutic approaches. View Full-Text
Keywords: glioblastoma; GSCs; Notch signaling pathway; new therapeutic approaches glioblastoma; GSCs; Notch signaling pathway; new therapeutic approaches
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Bazzoni, R.; Bentivegna, A. Role of Notch Signaling Pathway in Glioblastoma Pathogenesis. Cancers 2019, 11, 292.

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