UVB represses melanocyte cell migration and acts through β-catenin

被引:14
作者
Bertrand, Juliette U. [1 ,2 ,3 ]
Petit, Valerie [1 ,2 ,3 ]
Hacker, Elke [4 ]
Berlin, Irina [1 ,2 ,3 ]
Hayward, Nicholas K. [4 ]
Pouteaux, Marie [1 ,2 ,3 ]
Sage, Evelyne [1 ,2 ,3 ]
Whiteman, David C. [4 ]
Larue, Lionel [1 ,2 ,3 ]
机构
[1] PSL Res Univ, Inst Curie, INSERM, U1021,Normal & Pathol Dev Melanocytes, Orsay, France
[2] Univ Paris Saclay, Univ Paris Sud, CNRS UMR 3347, Orsay, France
[3] Equipe Labellisee Ligue Canc, Orsay, France
[4] Queensland Inst Med Res, Brisbane, Qld, Australia
关键词
BIO inhibitor; CHIR99021; inhibitor; human skin; iCRT3; mouse skin; p38; EXPRESSION; ACTIVATION; MUTATIONS; KINASE; PIGMENTATION; PATHWAY; PHOSPHORYLATION; PROLIFERATION; INACTIVATION; RADIATION;
D O I
10.1111/exd.13318
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100227 [皮肤病学];
摘要
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. beta-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 beta-catenin in the melanocyte lineage. We report that in vivo, UVB induces cytoplasmic/nuclear relocalization of beta-catenin in melanocytes of newborn mice and adult human skin. In mouse melanocyte and human melanoma cell lines in vitro, UVB increases beta-catenin stability, accumulation in the nucleus and cotranscriptional activity, leading to the repression of cell motility and velocity. The activation of the beta-catenin signalling pathway and its effect on migration by UVB are increased by an inhibitor of GSK3 beta, and decreased by an inhibitor of beta-catenin. In conclusion, UVB represses melanocyte migration and does so by acting through the GSK3-beta-catenin axis.
引用
收藏
页码:875 / 882
页数:8
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