Identifying Cell-Intrinsic Mechanisms of Melanoma Suppression by APOE Variants

Melanoma is a relatively uncommon form of skin cancer, but it is responsible for most skin cancer deaths because of its ability to metastasize, or spread throughout the body. In recent years many promising new treatments for melanoma have been developed, but most melanomas that have metastasized are still incurable. Therefore, we are particularly interested in understanding how melanoma cells leave the skin and travel to distant organs. We previously discovered that a protein called apolipoprotein E (APOE) helps slow the spread of melanoma cells in the body. There are three common types of APOE that every person is born with, which are called APOE2, APOE3, and APOE4. We recently found that these APOE types are not equal in their ability to slow melanoma spread, partly because the APOE4 version is best at activating the immune system to fight melanoma. However, we also know that melanoma cells in a dish behave less aggressively when treated with APOE4 compared to APOE2, even when immune cells are not present. This means that the APOE types have a direct effect on the melanoma cells themselves. Therefore, we believe that the APOE types differ in their ability to block a pro-cancer program that is active within melanoma cells. The goal of this project is to identify that program and therefore provide a new target for melanoma therapy.