Exploring the role of the mitochondrial chaperone TRAP1 in melanoma cell tumorigenicity

Cutaneous melanoma is the deadliest type of skin cancer originating from the malignant transformation of melanocytes. A key feature of melanoma is the hyperactivation of the MAP Kinase pathway that contribute to resulting increased cell survival, proliferation, metabolic adaptation and metastasis. Despite advances in therapies, melanoma treatment remains limited by drug resistance acquisition, underscoring the need for the discovery of new pharmacological targets. Here, we studied the role of the mitochondrial chaperone TRAP1, a well-known regulator of tumor metabolism in cancers with dysregulation of the Ras-ERK pathways. The analysis of bulk RNA-seq data from the TCGA melanoma dataset revealed that high TRAP1 expression correlates with enhanced metabolic signatures and reduced overall survival. Accordingly, genetic silencing of TRAP1 in both human and murine melanoma cells markedly reduces their neoplastic growth. My observations indicate a key role for TRAP1 in regulating melanoma metastasis, as its absence in human metastatic and patient-derived cell lines strongly impairs their migratory phenotype. Altogether, my data identify TRAP1 as a critical regulator of melanoma progression, setting it as a new potential pharmacological target.