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Updated: Dec 29, 2025
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Pro-metastatic functions of Notch signaling is mediated by CYR61 in breast cells
Mustafa Ilhan1, Cansu Kucukkose1, Eda Efe1
1Department of Molecular Biology and Genetics, Izmir Institute of Technology, 35430, Izmir, Turkey.
Abstract:
Metastasis is the main cause of cancer related deaths, and unfolding the molecular mechanisms underlying metastatic progression is critical for the development of novel therapeutic approaches. Notch is one of the key signaling pathways involved in breast tumorigenesis and metastasis. Notch activation induces pro-metastatic processes such as migration, invasion and epithelial to mesenchymal transition (EMT). However, molecular mediators working downstream of Notch in these processes are not fully elucidated. CYR61 is a secreted protein implicated in metastasis, and its inhibition by a monoclonal antibody suppresses metastasis in xenograft breast tumors, indicating the clinical importance of CYR61 targeting. Here, we aimed to investigate whether CYR61 works downstream of Notch in inducing pro-metastatic phenotypes in breast cells. We showed that CYR61 expression is positively regulated by Notch activity in breast cells. Notch1-induced migration, invasion and anchorage independent growth of a normal breast cell line, MCF10A, were abrogated by CYR61 silencing. Furthermore, upregulation of core EMT markers upon Notch1-activation was impaired in the absence of CYR61. However, reduced migration and invasion of highly metastatic cell line, MDA MB 231, cells upon Notch inhibition was not dependent on CYR61 downregulation. In conclusion, we showed that in normal breast cell line MCF10A, CYR61 is a mediator of Notch1-induced pro-metastatic phenotypes partly via induction of EMT. Our results imply CYR61 as a prominent therapeutic candidate for a subpopulation of breast tumors with high Notch activity.
Insights
Notch signaling promotes breast cancer metastasis by upregulating CYR61. Silencing CYR61 blocked Notch1-induced pro-metastatic phenotypes and epithelial-mesenchymal transition (EMT) in normal breast cells.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Metastasis is a leading cause of cancer mortality, necessitating research into its underlying molecular mechanisms.
- The Notch signaling pathway plays a crucial role in breast cancer development and metastasis.
- Understanding downstream mediators of Notch signaling is vital for developing new therapies.
Purpose of the Study:
- To investigate if CYR61 functions downstream of Notch signaling in promoting pro-metastatic phenotypes in breast cells.
- To elucidate the role of CYR61 in Notch-induced migration, invasion, and epithelial-mesenchymal transition (EMT).
Main Methods:
- Assessed CYR61 expression in response to Notch activity in breast cells.
- Utilized CYR61 silencing to evaluate its role in Notch1-induced pro-metastatic phenotypes (migration, invasion, anchorage-independent growth) in MCF10A cells.
- Examined the impact of CYR61 absence on EMT markers following Notch1 activation.
- Investigated CYR61's role in Notch inhibition-induced effects on migration and invasion in MDA MB 231 cells.
Main Results:
- Notch activity positively regulated CYR61 expression in breast cells.
- CYR61 silencing abrogated Notch1-induced migration, invasion, and anchorage-independent growth in MCF10A cells.
- Notch1-induced upregulation of core EMT markers was impaired without CYR61.
- CYR61 downregulation was not essential for Notch inhibition-induced reduction in migration and invasion in MDA MB 231 cells.
Conclusions:
- CYR61 mediates Notch1-induced pro-metastatic phenotypes in normal breast cells, partly through EMT induction.
- CYR61 is a potential therapeutic target for breast tumors with high Notch activity.
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