title: UVB represses melanocyte cell migration and acts through β-catenin.
abstract: 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.
authors.affiliation: Institut Curie, PSL Research University, INSERM U1021, Normal and Pathological Development of Melanocytes, Orsay, France.|Univ Paris-Sud, Univ Paris-Saclay, CNRS UMR 3347, Orsay, France.|Equipe Labellisée Ligue Contre le Cancer, Orsay, France.
authors.forename: Juliette U
authors.initials: JU
authors.lastname: Bertrand
authors.affiliation: Institut Curie, PSL Research University, INSERM U1021, Normal and Pathological Development of Melanocytes, Orsay, France.|Univ Paris-Sud, Univ Paris-Saclay, CNRS UMR 3347, Orsay, France.|Equipe Labellisée Ligue Contre le Cancer, Orsay, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Petit
authors.affiliation: Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors.forename: Elke
authors.initials: E
authors.lastname: Hacker
authors.affiliation: Institut Curie, PSL Research University, INSERM U1021, Normal and Pathological Development of Melanocytes, Orsay, France.|Univ Paris-Sud, Univ Paris-Saclay, CNRS UMR 3347, Orsay, France.|Equipe Labellisée Ligue Contre le Cancer, Orsay, France.
authors.forename: Irina
authors.initials: I
authors.lastname: Berlin
authors.affiliation: Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.affiliation: Institut Curie, PSL Research University, INSERM U1021, Normal and Pathological Development of Melanocytes, Orsay, France.|Univ Paris-Sud, Univ Paris-Saclay, CNRS UMR 3347, Orsay, France.|Equipe Labellisée Ligue Contre le Cancer, Orsay, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Pouteaux
authors.affiliation: Institut Curie, PSL Research University, INSERM U1021, Normal and Pathological Development of Melanocytes, Orsay, France.|Univ Paris-Sud, Univ Paris-Saclay, CNRS UMR 3347, Orsay, France.|Equipe Labellisée Ligue Contre le Cancer, Orsay, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Sage
authors.affiliation: Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Whiteman
authors.affiliation: Institut Curie, PSL Research University, INSERM U1021, Normal and Pathological Development of Melanocytes, Orsay, France.|Univ Paris-Sud, Univ Paris-Saclay, CNRS UMR 3347, Orsay, France.|Equipe Labellisée Ligue Contre le Cancer, Orsay, France.
authors.forename: Lionel
authors.identifier: 0000-0002-2010-6107
authors.initials: L
authors.lastname: Larue
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes; D008544:Melanocytes / Q000502:physiology / Q000528:radiation effects*; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation / Q000528:radiation effects; D021381:Protein Transport / Q000528:radiation effects*; D015398:Signal Transduction / Q000528:radiation effects; D014466:Ultraviolet Rays; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse
keywords: BIO inhibitor; CHIR99021 inhibitor; human skin; iCRT3 inhibitor; mouse skin; p38