INTERNATIONAL CONGRESS OF
PharmacoGenetics
Notch Signaling Pathway in Breast Cancer
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Mehrdad Ostadpoor,1,* Ahmad Zeinodini,2 Pooria Rezaei,3
1. Graduated of Veterinary Medicine Faculty, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
2. Graduated of Veterinary Medicine Faculty, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
3. Graduated of Veterinary Medicine Faculty, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
- Introduction: Breast cancer is the most common cancer and also the primary cause of mortality due to cancer in female around the World. The Notch signaling system is the critical fundamental pathway, a unique cellular program that is encountered in cell type specification and organ development. It is the main regulator of cell destination and differentiation. Notch signaling is dysregulated in multiple cancer types. Canonical notch signaling is initiated by the interaction between a notch ligand and notch transmembrane receptor on the surface of a neighboring cell. In mammals, the notch pathway consists of four equivalent receptors (NOTCH1-NOTCH4) and five ligands, including three Delta-like proteins (DLL-1, 2 and 4) and two Jagged proteins (Jagged-1 and Jagged-2).
- Methods: In the current study, keywords including Notch Signaling, Breast Cancer, and Progression were reviewed from the list of Mesh and other credible websites including PubMed, Science Direct and Google Scholar and the data was organized. The searches comprised all published paper from 2010 to 2022. All of full text was considered and the papers manifested as only abstract was excluded. The full papers selected that specific prognostic role of notch signaling pathway in breast cancer only. Totally 50 papers were selected and studied in this review.
- Results: Articles have been shown that notch is an oncogene in the breast, as overexpression of Notch1IC, Notch3IC, or Notch4IC is sufficient for transformation of normal breast epithelial cells into cancer cells. Also, notch signaling contributes significantly to cell survival, proliferation, differentiation, apoptosis, tissue patterning, cell-fate decision, and morphogenesis. However, its dysregulation and role in promoting cellular transformation has led to further investigations of the role of notch in a variety of cancers. Moreover, in one clinical study expression of the notch receptors and their ligands was found to be highly elevated in breast cancer tissues and correlated with poor survival of human breast cancer patients. Several studies have established that notch signaling exhibits its oncogenic properties through its interactions with other signaling pathways, such as Ras, TGFβ, and Wnt in the mammary gland tumorigenesis. Also, upregulated notch expression was found in breast cancer stem cell and initiating cell populations characterized by phenotypic markers CD44+/CD24−, and was linked to tumor-initiating properties and cancer stem cells-like invasive features. Numerous articles concluded notch signaling promotes proliferation in breast cancer cell lines by upregulating cyclin A, cyclin B, and cyclin D1 expression. Moreover, Notch protects breast epithelial cells from apoptosis by activating Akt. In breast cancer cells, Notch1 or Notch4 can promote the expression of Slug by activating the Slug promoter. In several recent studies NOTCH3 signaling was shown to promote the growth of basal breast cancers in functional studies.
- Conclusion: In mammals, there is clinical and laboratory evidence that the notch family is clearly implicated in human breast cancer in different combinations. The Notch pathway masters and maintains a balance between cell multiplication, differentiation, and programmed cell death, but the mis- regulated notch ligand-receptor interaction in breast cancer gives the spark for tumor growth initiation, progression, and maintenance by inducing aberrant tumorigenesis.
- Keywords: Notch Signaling, Breast Cancer, Progression
