Author(s): Kasidy Estheimer, Karsyn Cannon, A. Paulina Medelin
Mentor(s): Gennie Parkman, Sheri Holmen
Institution Weber
Brain metastases are a major complication of metastatic melanoma, contributing to nearly half of melanoma-related deaths. The presence of brain metastasis worsens prognosis, with median survival under 2 years. Therefore, understanding the mechanisms driving melanoma brain metastasis is critical. One such mechanism is the activation of the AKT signaling pathway, which promotes disease progression. Previous research in the Holmen lab has shown that AKT activates focal adhesion kinase (FAK) and inhibiting either AKT or FAK reduces tumor cell invasion. FAK is a critical regulator of cell adhesion, migration, and invasion, processes essential for cancer metastasis. In this study, we tested the functional impact of various activating and inactivating mutations of FAK in melanoma cell lines to assess their roles in tumor progression and metastasis. We introduced two activating mutations—Y397E (mimicking phosphorylation) and ΔN-FAK (a truncated form retaining kinase activity)—and one inactivating mutation, K454R (a kinase-dead mutation), into melanoma cell lines and are testing them for the ability to influence the migration and invasion of these cell lines in vitro. In addition, these cell lines are being tested in vivo for their roles in promoting tumor growth and metastasis. Collectively, these findings will provide a greater understanding of the role of FAK activity in melanoma metastasis.