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In the UK, 12,000 patients die from metastatic breast cancer annually. There is therefore an urgent need to identify the molecules that cause metastasis. Recent work has revealed a role for the RUNX family of transcription factors in the development of metastatic breast cancer. The RUNX proteins form active transcription factor complexes when bound by the heterodimeric partner CBFβ to regulate the expression of metastatic genes. Previous work from our laboratory has demonstrated that knockdown of CBFβ resulted in a decreased invasion capacity of the metastatic breast cancer cell line MDA-MB-231. Three-dimensional culture of MDA-MB-231 cells revealed that loss of CBFβ induces a mesenchymal to epithelial transition (MET). The aim of this project was to determine the role of the RUNX/CBFβ complex in maintaining the mesenchymal phenotype of metastatic breast cancer cells. The data presented show that the phenotype changes were accompanied by changes in EMT marker-gene expression, including Snai2, MMP9, and MMP13. Induction of CBFβ in the CBFβ-knockdown cells remarkably restored both the invasive capacity and the mesenchymal phenotype. Further analysis revealed that maintenance of the mesenchymal phenotype was dependent upon both CBFβ-partner proteins, RUNX1 and RUNX2. Taken together the data presented in this thesis demonstrate that RUNX/CBFβ complexes drive the epithelial to mesenchymal transition (EMT) in breast cancer cells. These findings are likely to be important in the development of potential therapies to inhibit the metastatic spread of breast cancer.

Like many other decayed downtown areas in the U.S, the one in Montgomery, AL has a pedestrian framework which was provided for walking at the beginning of its settlement. However, most of the downtown neighborhood streets and roads are now used primarily for automobiles. Furthermore, numerous vacant spaces and degraded buildings and structures are left because of the rise of personal automobiles and the consequent urban sprawl. The limitation of life in Montgomery Alabama, where some people need to drive a long way for working or tourism and some people who have no cars have to go out for work and shopping, can be addressed through appropriate urban public pattern design. This project attempts to find more options for people to use the downtown area and live a better life, drawing on existing physical and cultural conditions. It seeks to get rid of the limitation of the excessive automobile-based development and return to the city what people and the world really want and need. The project achieved this by establishing a new pattern system of green public spaces made up of existing overlooked spaces that connect with specific uses in the urban area. This new pedestrian network will provide more options for people to move around, and new patterns of living in the decayed downtown. The objective of the research is both to save an area which is going to die and reduce people’s dependence on cars.