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Published on: January 12, 2020
Contradictory Effect of Notch1 and Notch2 on Phosphatase and Tensin Homolog and its Influence on Glioblastoma
Mostafa Shabani1,2, Hamid Taghvaei Javanshir1,2, Ahmad Bereimipour2,3
1Medical Genomics Research Center, Tehran Medical Sciences Islamic Azad University, Tehran, Iran.
Abstract:
Many genes induce angiogenesis in tumors, and among them, Notch family genes have received particular attention due to their extensive network of connections with other genes active in this function. Suppression of angiogenic signaling has been studied in various cancers, confirming Notch's fundamental and extensive role. According to studies, four Notch genes work independently with many genes such as vascular endothelial growth factor, phosphatase and tensin homolog, Phosphoinositide 3-kinase/Akt, and matrix metalloproteinases, and so many other genes, as well as proteins (such as hypoxia-inducible factor-1 alpha) significantly affect tumor angiogenesis. Notch1 regular activity in a healthy person causes angiogenesis in body tissues, controlled by normal Notch2 activity. However, in many cases of glioblastoma, whether on patients or tumor xenografts or in vivo models, a mutation in one of these two essential genes or at least one of the genes and proteins that affected by them can cause better angiogenesis in hypoxic conditions and lead to become an invasive tumor. In this review, we examined the contrasting activity of Notch1 and Notch2 and the signaling cascade that each generates in the angiogenesis of glioblastoma, the most invasive cancer of the central nervous system.
Insights
Notch1 and Notch2 genes play critical roles in tumor angiogenesis, particularly in glioblastoma. Mutations in these genes can promote invasive tumor growth by enhancing blood vessel formation in low-oxygen conditions.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Notch family genes are key regulators of tumor angiogenesis, interacting with numerous signaling pathways.
- Vascular endothelial growth factor, Akt, and hypoxia-inducible factor-1 alpha are among the critical factors influenced by Notch signaling in cancer.
Purpose of the Study:
- To review the distinct roles of Notch1 and Notch2 in glioblastoma angiogenesis.
- To elucidate the signaling cascades generated by Notch1 and Notch2 in the context of the central nervous system's most invasive cancer.
Main Methods:
- Literature review focusing on Notch signaling in glioblastoma.
- Analysis of gene interactions and protein pathways involved in tumor angiogenesis.
- Examination of studies on patients, tumor xenografts, and in vivo models.
Main Results:
- Notch1 and Notch2 exhibit contrasting activities in glioblastoma angiogenesis.
- Mutations in Notch1 or Notch2 can enhance angiogenesis under hypoxic conditions, promoting tumor invasiveness.
- These genes interact with multiple pathways crucial for tumor vascularization.
Conclusions:
- Notch1 and Notch2 signaling pathways are central to glioblastoma angiogenesis.
- Understanding the differential roles of Notch1 and Notch2 is vital for developing targeted therapies against glioblastoma.
- Targeting Notch signaling offers a potential strategy to inhibit the growth and invasiveness of glioblastoma.
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