Deciphering key steps in the metastatic process of breast cancer by focusing on the role of MAFF
Second Supervisor: Dr Eileen Parkes
Breast cancer is the most common cancer in women, which has a high mortality rate in the UK. Tumour metastasis from breast cancer is associated with a poor prognosis due to its aggressiveness and limited treatment options. The unique interaction between breast cancer cells and the unique microenvironment of distant organs further promotes tumour metastasis. There is therefore a critical need to understand the molecular mechanisms of this pathogenesis to find a new and more effective treatment in clinic. The v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) gene is a hypoxia-regulated gene, which we have previously demonstrated is crucial in tumour invasion and metastasis. From RNA sequencing, we have further found that MAFF regulates genes specific for lung and bone metastasis. Interestingly, our preliminary study with the metastatic MDA-MB-231 cell line supports these findings by showing elevated levels of MAFF and IL11 when compared to the parental MDA-MB-231 cell line. In this study, we will therefore investigate, using a recently established mouse metastasis model, the role of MAFF in tumour metastasis as a potentially targetable mechanism in breast cancer.
We will work using basic science to preclinical science techniques. Specifically, by focusing on tumour invasion and metastasis, we will identify key factors that can be targeted or be used as a diagnostic marker. The student will be trained to perform basic cell and molecular biology as well as mouse work including western blot, qRT-PCR, invasion assay, chromatin immunoprecipitation, mouse xenograft studies, and immunohistochemistry. In addition, through weekly departmental seminars, journal clubs, and manuscript review, skills for presentation, data management, and scientific writing will be trained.
Moon, E.J., Mello, S.S., Li, C.G., Chi, J.T., Thakkar, K., Kirkland, J.G., Lagory, E.L., Lee, I.J., Diep, A.N., Miao, Y. and Rafat, M., 2021. The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling. Nature communications, 12(1), p.4308.