| Description |
Melanoma is a form of skin cancer that arises from the uncontrolled growth of melanocytes. Melanoma is not the most common form of skin cancer, but its ability to metastasize to other parts of the body makes it more life-threatening than others [1]. Despite the success of new FDA-approved therapies, the development of brain metastases is one of the primary causes of treatment failure. Understanding the mechanisms leading to melanoma metastasis development will allow for novel therapeutic options to improve the overall survival of individuals with melanoma, specifically when there has been metastasis to the brain. It has been discovered that concurrent interplay between signaling pathways including the mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3'- kinase/protein kinase B (PI3K/AKT) pathways lead to metastasis of melanoma [2, 3]. Focal adhesion kinase (FAK) is a signaling protein in the PI3K/AKT pathway that functions to regulate and control cell motility and invasion. A publication by Kircher et al. was the first to describe a mechanism whereby the AKTE17K hotspot mutation promotes melanoma brain metastasis through activation of downstream FAK. This mechanism, however, had yet to be demonstrated experimentally. Based on these findings, we aimed to determine whether activation of FAK recapitulates the metastatic phenotype of AKT1 activation. We evaluated the role of FAK in tumor progression and metastasis by utilizing an autochthonous mouse model of melanoma that combines expression of activated FAK with mutant BRAF and loss of tumor suppressor genes Cdkn2a and Pten. We assessed potential metastasis to distant organs by determining the presence of lesions in the tissues collected from our mouse model. Expression of activated FAK phenocopies the expression of activated AKT1 as assessed by tumor penetrance, latency, and metastasis. Because AKT inhibitors in the clinic have historically resulting in considerable toxicity, FAK inhibition may represent a safer therapeutic alternative to improve the survival of patients with metastatic melanoma. |
