Grant: Project Grant

Breast cancer is the most common cancer affecting women and is the second-leading cause of cancer-related deaths in these patients. The most devastating aspect of breast cancer is the development of metastatic disease. The term "metastasis" refers to the ability of cancer cells to leave the organ/tissue in which they first form and spread to distant sites in the body. Common sites of metastasis in patients with breast cancer include the lungs and liver. Thus, it is essential that we learn more about how breast cancer cells are able metastasize. We have identified a protein called Afadin, which functionally contributes to the ability of breast cancer cells to form distant metastases. Afadin is a complicated protein, with some studies suggesting that high Afadin expression is associated with better survival in breast cancer patients. In contrast, our results suggest that in a particular subtype of breast cancer, high levels of Afadin are associated with poor overall and metastasis-free survival. Interestingly, our data show that Afadin promotes the ability of breast cancer cells to form lung and liver metastases. These data highlight the complex roles that Afadin plays in modulating the metastatic ability of breast cancer cells. In this grant application, we will determine the cellular and molecular mechanisms that are engaged by Afadin to promote the formation of lung and liver metastases. We will also investigate the reasons why Afadin can act as a metastasis promoter in one instance and a metastasis suppressor in another context. Completion of the proposed experiments will provide an in-depth understanding of how Afadin regulates breast cancer metastasis. Ultimately, this information will be used to devise new therapeutic strategies to better clinically manage breast cancer patients with metastatic disease.