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. 2020 Jul 22;10:12129. doi: 10.1038/s41598-020-68945-9

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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(A) Pigmentation regulation by alpha-melanocyte stimulating hormone (MSHα) and G-proteins from melanocortin receptor 1 (MC1R): MSHα/MCR1 can trigger the activation of the adenylate cyclase (ADCY) and 3′–5′-cyclic adenosine monophosphate AMP (cAMP). The cAMP signals activate the protein kinase A (PKA) that phosphorylates and activates cAMP responsive element binding protein (CREB) transcription factor, which induces the expression of melanocyte inducing transcription factor (MITF) and induction of proliferation and differentiation of melanocytes. G-proteins: β, γ, and α; ATP: adenosine triphosphate. (B) Kaplan–Meier (K-M) curves for progression-free survival according to ADCY3 c.675+9196T>G genotypes, where patients with TT genotype presented lower survival than those with TG or GG genotype. (C) K-M curves for melanoma-specific survival according to MITF c.938-325G>A genotypes, where patients with GA or AA genotype presented lower survival than those with GG genotype.