The exposure of skin to ultraviolet (UV) radiation can have both beneficial and deleterious effects: it can lead, for instance, to increased pigmentation and vitamin D synthesis but also to inflammation and skin cancer. UVB may induce genetic and epigenetic alterations and have reversible effects associated with post-translational and gene regulation modifications. β-catenin is a main driver in melanocyte development; although infrequently mutated in melanoma, its cellular localization and activity are frequently altered. Here, we evaluate the consequence of UVB on β-catenin in the melanocyte lineage. We report that in vivo, UVB induces cytoplasmic/nuclear relocalization of β-catenin in melanocytes of newborn mice and adult human skin. In mouse melanocyte and human melanoma cell lines in vitro, UVB increases β-catenin stability, accumulation in the nucleus and cotranscriptional activity, leading to the repression of cell motility and velocity. The activation of the β-catenin signalling pathway and its effect on migration by UVB are increased by an inhibitor of GSK3β, and decreased by an inhibitor of β-catenin. In conclusion, UVB represses melanocyte migration and does so by acting through the GSK3-β-catenin axis.
Keywords: BIO inhibitor; CHIR99021 inhibitor; human skin; iCRT3 inhibitor; mouse skin; p38.
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