Abstract 2027: Understanding the role and regulation of newly synthesized Annexin A2 in the progression of breast cancer

In Ireland, almost three thousand women are diagnosed with invasive breast cancer every year. This makes it the most common form of malignant tumour found in Irish females and accounts for 17% of all female cancer deaths. Although treatment for breast cancer when diagnosed early is highly effective, for those who develop late stage and metastatic breast cancer, survival rates decline rapidly. As a result, a large effort is being made to understand the mechanisms involved in the progression of breast cancer and identifying the changes that take place during the in-situ to metastatic transition. Using 2-D and 3-D in vitro models of cancer metastasis, we conducted a mass spectrometry screen to identify proteins that are newly synthesised by breast cancer cells as they migrate towards a growth factor gradient. From this screen, we identified Annexin A2 as a newly synthesised protein. Annexin A2 is a calcium-ion regulated, phospholipid-binding protein, which is involved in cell trafficking, cell-to- cell contact, cell motility and regulation of the cytoskeletal structure. Annexin A2 has been reported to be overexpressed in a range of cancers including breast cancer and has also been reported to contribute to cancer-associated processes such as proliferation, migration and chemoresistance. While investigating the role of Annexin A2 in the progression of breast cancer, our findings suggest that through modulation of the cell culture environment, subjecting cells to stress conditions and altering growth factor supplementation, that the intracellular expression of Annexin A2 remains relatively constant. However, in breast cancer patients we see dysregulation of Annexin A2 expression at a gene level, which correlates with disease progression. We are currently investigating how alterations in the composition of the extracellular environment, particularly the extracellular matrix, regulates Annexin A2 expression and cellular location. We believe that delineating the function of newly synthesised proteins such as Annexin A2 has the potential to direct novel anti-cancer therapies aimed specifically at halting the progression of breast cancer. Ultimately, these insights may lead to improvements in survival rates for those affected with this disease. Citation Format: Amira F. Mahdi, Beatrice Malacrida, Joanne Nolan, Kieran McGourty, Aoife J. Lowery, Patrick A. Kiely. Understanding the role and regulation of newly synthesized Annexin A2 in the progression of breast cancer