Investigating the role of P-Rex1 in mouse models of melanoma

The skin cancer malignant melanoma (MM) is increasing in rate more than any other common cancer in the UK, and is doubling in rate every 10-20 years in Western countries. Early spread of MM to other organs is nearly always the cause of death from this cancer. Identifying and studying new proteins which are both responsible for this spread and treatable is crucial for this cancer which is known for being unresponsive to traditional therapies. We have genetically removed a protein called P-Rex1 from black mice, and discovered that their bellies and feet remain white. These white areas suggest that melanocytes (the skin cells responsible for MM) aren‘t reaching the furthest regions of migration during normal mouse development. We also know that the genetic changes required for melanocyte movement during development are very similar to the genetic changes required during MM tumour spread. Therefore we have obtained mice which develop human-like melanomas and I plan to assess if removing P-Rex1 can stop the lethal migration of melanocytes (known as metastasis) to other organs. I will also analyse resected human melanoma specimens to evaluate P-Rex1 in a comprehensive manner which is correlated with how well the patient did with their melanoma.