Project 466541

Uveal melanoma is the most common cancer of the eye. Every year, approximately 130 Canadians are diagnosed with uveal melanoma, which kills approximately half of patients within 1 year due to uncontrolled spread of cancer cells to the lungs, liver, and/or bones. In 80% of these malignant cases, there is a mutation in a gene called BAP1. Previous research suggests that BAP1 mutations lead to epithelial to mesenchymal transition (EMT), a process which allows many cancer cells to gain migratory and invasive properties. Our lab has developed a Bap1 mutant uveal melanoma mouse model that results in accelerated cancer spread to the lungs and liver. Our preliminary data suggests that Bap1 mutations prevent cells from ;sticking to one another, which may allow the cancer cells in the eye to travel to distant sites. The goal of my research is understand how Bap1 loss leads to this spread of cancer cells from the primary tumour in the eye to the lungs and liver. Using our mouse model, I will study the expression of a group of proteins part of the Apical Junction Complex (AJC), which help neighbouring cells stick to one another. I will determine which cells in the tumour are decreasing the expression of the AJC proteins and examine the relationship between the amount and distribution of AJC protein expression and molecular signs of tumour aggressiveness. Through this work, I hope to identify potential therapeutic targets to mitigate or prevent uveal melanoma spread, thus improving patient outcomes.