(1) Service de Dermatologie, Centre Hospitalier Universitaire, Besançon, France
(2) Department of Dermatology, Joan and Sanford I.Weill Medical College of Cornell University, New York, United States of America
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Cyclic adenosine monophosphate (cAMP) is a second messenger signalling molecule, present from bacteria to man, involved in many cellular functions. Pathways mediated by cAMP signalling are widespread in the body. cAMP plays a role in both normal physiology and in various diseases such as cancer. In melanoma, cAMP signalling can either activate or inhibit growth thereby leading to conflicting results. In many cases the same cAMP signalling proteins such as melanocortin 1 receptor (MC1R), protein kinase A (PKA), and phosphodiesterases (PDEs) are involved in both growth stimulation and inhibition begging the question how cAMP can seemingly lead to disparate cellular events in melanoma via the same signalling cascade. Recently, it has become clear that cAMP signals in discrete microdomains capable of responding to distinct upstream signals and, via identical protein machinery, can induce unique cellular events. The complex role of cAMP signalling in melanoma supports an important role for cAMP microdomains in melanoma biology. The aim of this review was to discuss how diverse effects of cAMP signalling in melanoma support the role of distinct cAMP microdomains in melanomagenesis, metastasis, and resistance to therapy.
Further research is warranted to elucidate the impact of contextual cues and intrinsic cell type differences on the role of cAMP signaling in melanoma, in order to better understand melanomagenesis, metastasis, and resistance and to help identify new therapeutic targets.