Fig. 1

A Physiological condition. B Pathological condition (advanced stage melanoma). In physiological condition melanocytes express a membrane receptor (MC1R) that controls the melanin synthesis process. A Upon UV exposure, alpha-melanocyte stimulating hormone (α-MSH) is released by keratinocytes: the binding of α-MSH to MC1R activates Adenyl Ciclase (AC) that stimulates cilic AMP (cAMP) production and the activation of Protein Kinase A (PKA). PKA phosphorylates the transcription factor CREB that stimulates the transcription factor MiTF which in turn promotes the expression of melanogenesis enzyme genes TYR, TRP1 and DCT. In our working hypothesis B in advanced stage of melanoma, tumour cells overexpress MC1R and BRAF inhibitor treatment significantly increase this MC1R expression via MiTF-dependent pathways, leading to enhanced ligand binding on the cell surface. As a consequence, the cAMP/PKA pathway is aberrantly altered and might promote tumour migration , growth and proliferation. PM: Plasmatic Membrane; Gα, Gβ, Gγ: G proteins; CREB: cAMP Response Element Binding protein; RTK Tyrosine Kinase Receptor. This figure was created with www.BioRender.com