It is well established that the Wnt pathway is associated with tumorigenesis in a wide range of human cancers, including a majority of breast cancers. However, due to diverse roles of Wnt signalling, therapeutic targeting has not yielded consistent results and underlying mechanisms remain unclear. Here, I show that breast cancer cell lines with high E-cadherin expression are resistant to TCF4 inhibitors and develop cancer stem cell characteristics. Conversely, cells with low levels of E-cadherin are very susceptible to cell death with the same treatment. My results suggest that breast cancer cells in an epithelial-like state, but not mesenchymal-like state, will be more responsive to therapeutic targeting of the Wnt/TCF pathway. Importantly, E-cadherin high cells show robust Akt activation, whereas E-cadherin low cells do not. Thus, combinational inhibition of both Wnt and Akt signalling is needed to effectively target breast cancer cells in both the epithelial and mesenchymal states.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/32961 |
| Date | January 2015 |
| Creators | Ooi, Sarah |
| Contributors | Wang, Lisheng |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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