The authors identified KMT2D as a potent tumor suppressor in melanoma through an in vivo epigenome-focused pooled RNAi screen and confirmed the finding by using a genetically engineered mouse model based on conditional and melanocyte-specific deletion of KMT2D.
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Maitituoheti, M., Keung, E. Z., Tang, M., Yan, L., Alam, H., Han, G., Singh, A. K., Raman, A. T., Terranova, C., Sarkar, S., Orouji, E., Amin, S. B., Sharma, S., Williams, M., Samant, N. S., Dhamdhere, M., Zheng, N., Shah, T., Shah, A., … Rai, K. (2020). Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma. Cell Reports, 33(3). https://doi.org/10.1016/j.celrep.2020.108293 Cite
Investigators report on a facile protocol for the efficient isolation and enrichment of pure populations of human limbal melanocytes by fluorescence-activated cell sorting using antibodies raised against the cell surface marker CD117.
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Arp3 depletion in the melanocyte lineage resulted in severe pigmentation defects in dorsal and ventral regions of the mouse skin.
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Scientists described ways to overcome obstacles in the context of normal human skin, thus offering a glimpse into the genomic landscapes of individual melanocytes from human skin.
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Tang, J., Fewings, E., Chang, D., Zeng, H., Liu, S., Jorapur, A., Belote, R. L., McNeal, A. S., Tan, T. M., Yeh, I., Arron, S. T., Judson-Torres, R. L., Bastian, B. C., & Shain, A. H. (2020). The genomic landscapes of individual melanocytes from human skin. Nature, 1–6. https://doi.org/10.1038/s41586-020-2785-8 Cite
The authors showed that downregulation of galcb, a zebrafish orthologue of human beta-galactosylceramidase (GALC), affects melanoblast and melanocyte differentiation in zebrafish embryos, suggesting a possible role for GALC in melanoma.
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Belleri, M., Paganini, G., Coltrini, D., Ronca, R., Zizioli, D., Corsini, M., Barbieri, A., Grillo, E., Calza, S., Bresciani, R., Maiorano, E., Mastropasqua, M. G., Annese, T., Giacomini, A., Ribatti, D., Casas, J., Levade, T., Fabrias, G., & Presta, M. (2020). Beta-Galactosylceramidase Promotes Melanoma Growth Via Modulation of Ceramide Metabolism. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-19-3382 Cite
The authors focus on how neurohormones impact human skin physiology and pathology. They highlight basic concepts, major open questions, and translational research perspectives in cutaneous neuroendocrinology and argue that greater emphasis on neuroendocrine human skin research will foster the development of novel dermatological therapies.
[Trends in Molecular Medicine]
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Investigators showed that NRF2 suppressed the activity of the melanocyte lineage marker MITF in melanoma, thereby reducing the expression of pigmentation markers.
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The authors investigate the association of exosomes with vitiligo and emphasize the role of exosomes in immune regulation, melanocyte–keratinocyte interactions, and melanogenesis.
The authors showed that melanocyte survival was mediated by diverse, nonredundant signaling pathways, including ERK1/2, AKT, PKA, and PKC.
The authors describe ectopic factors which drive human pluripotent stem cell differentiation to melanocytes in two dimension, as well as in organoid models.
Authors summarize current findings about CD271-associated mechanisms in melanoma cells and illustrate the role of CD271 for melanoma cell migration and metastasis, phenotype-switching, resistance to therapeutic interventions, and the maintenance of an neural crest stem cells-like state.