Importance of SPRED1 in melanoma

Proteins neurofibromin (NF1 gene product) and SPRED1 are important negative regulators of the RAS-MAPK signaling pathway, which is a key player in the development of cutaneous melanoma (CM). The role of NF1 in melanoma has already been studied, but the role of SPRED1 in CM remains to be clarified. We have obtained evidence that SPRED1 is a key suppressor in a subset of human CM. Since the physical interaction of neurofibromin with SPRED1 is essential for the function of neurofibromin, we hypothesize that SPRED1 mutated melanomas may phenocopy NF1 mutated melanomas. Patients with high NF1 expressing melanomas have a better overall survival than patients with low NF1 expressing melanomas. The same holds true for patients with high SPRED1 expressing melanomas. Therefore, we propose to genetically ablate SPRED1 during melanogenesis and melanomagenesis, and to study the consequences of this inactivation in human melanomas and in a Spred1 melanoma mouse model