NOTCH1 and Associated Diseases
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Overview of NOTCH1
In humans, neurogenic locus notch homolog protein 1 (NOTCH1) is a protein encoded by the NOTCH1 gene. NOTCH1 is a single-pass transmembrane receptor of the Notch family with typical structural characteristics of the type 1 transmembrane protein family such as a multiple epidermal growth factor-like repeats-contained extracellular domain, and an intracellular domain including multiple and different domains. NOTCH1 functions as a receptor for membrane-bound ligands and plays a critical role in a variety of developmental processes by regulating cell proliferation, cell differentiation, fate decisions, and survival.
NOTCH1 in Disease
Activation of Notch and increased NOTCH1 expression are correlative with tumor genesis such as prostate cancer, colon cancer, breast cancer, and so on. Diseases associated with NOTCH1 also include aortic valve disease 1.
- Breast cancer
NOTCH1 downregulation is associated with breast cancer (BC). One of the main causes of cancer-related death in women is breast cancer, and Notch signaling is critical in controlling cell proliferation and apoptosis. Previous studies show that overexpression of NOTCH1 is observed in both human BC cell lines and tissues. In human BC cells, siRNA-mediated knockdown of NOTCH1 can cause cell growth inhibition by inducing cell apoptosis via the inactivation of NF-κB signaling pathways. Besides, downregulated NOTCH1 is related to the increased chemosensitivity of BC cells. Taken together, NOTCH1 can be regarded as a potential target for BC treatment.
- Colon cancer
NOTCH1 signaling pathway positively regulates the growth of colon cancer (CC). Ectopic expression of NOTCH1 is associated with the development of CC, whose cells grow out of control. Upregulated expression of NOTCH1 is observed in CC tissues and the level of NOTCH1 expression is related to pathologic grade and progression. Knockdown of NOTCH1 can inhibit cell proliferation, colony formation, and tumorsphere formation and induce apoptosis and cell cycle arrest in CC cell lines. While overexpression of NOTCH1 can enhance cell proliferation, cell cycling, and tumorsphere formation in vitro and in vivo. Thus, for human CC, altering NOTCH1-related signaling may be a viable treatment.
Fig.1 Knockdown of NOTCH1 inhibits the colony formation of CC cell lines. (Zhang, 2010)
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References
- Ji. RNAi-mediated knockdown of Notch-1 leads to cell growth inhibition and enhanced chemosensitivity in human breast cancer. Oncol Rep. 2010, 23.
- Zhang, Y.; et al. NOTCH1 regulates the growth of human colon cancers. Cancer. 2010, 116: 5207–5218.
