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Retinoid-X-Receptors (α/β) in Melanocytes Modulate Innate Immune Responses and Differentially Regulate Cell Survival following UV Irradiation
Melanoma is the deadliest form of skin cancer. It derives from melanocytes, the melanin-producing cells of our skin, which give our skin its tone in addition to protecting it from harmful effects of ultraviolet radiation (UVR). Changes in the skin microenvironment, such as signaling from other cell types, can influence melanoma progression. While several key genes in melanoma development have been identified, the underlying mechanisms are complex; different combinations of mutations can result in melanoma formation and genetic profiles of tumors can vary greatly among patients. Therefore, identification of novel therapeutic targets is crucial. Our present study uses a tissue-specific gene ablation strategy to characterize a novel role of type II nuclear receptors [Retinoid-X-Receptors (RXRs)] in melanocytes to control UVR-induced skin immune responses and cell survival. Several of these observed changes are risk factors for melanoma progression and identify RXRs as potential drug targets for melanoma diagnosis, prevention, and treatment. This newly-discovered role of retinoid receptor signaling in immune surveillance can be studied in different types of cancer and in other diseases including metabolic syndromes and atherosclerosis. The identified pathway is ideal for targeting using specific ligands or small molecule modulators of RXR signaling in different cell types and tissues.
Vyšlo v časopise: Retinoid-X-Receptors (α/β) in Melanocytes Modulate Innate Immune Responses and Differentially Regulate Cell Survival following UV Irradiation. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004321
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004321Souhrn
Melanoma is the deadliest form of skin cancer. It derives from melanocytes, the melanin-producing cells of our skin, which give our skin its tone in addition to protecting it from harmful effects of ultraviolet radiation (UVR). Changes in the skin microenvironment, such as signaling from other cell types, can influence melanoma progression. While several key genes in melanoma development have been identified, the underlying mechanisms are complex; different combinations of mutations can result in melanoma formation and genetic profiles of tumors can vary greatly among patients. Therefore, identification of novel therapeutic targets is crucial. Our present study uses a tissue-specific gene ablation strategy to characterize a novel role of type II nuclear receptors [Retinoid-X-Receptors (RXRs)] in melanocytes to control UVR-induced skin immune responses and cell survival. Several of these observed changes are risk factors for melanoma progression and identify RXRs as potential drug targets for melanoma diagnosis, prevention, and treatment. This newly-discovered role of retinoid receptor signaling in immune surveillance can be studied in different types of cancer and in other diseases including metabolic syndromes and atherosclerosis. The identified pathway is ideal for targeting using specific ligands or small molecule modulators of RXR signaling in different cell types and tissues.
Zdroje
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Štítky
Genetika Reprodukčná medicína
Článek Ribosomal Protein Mutations Induce Autophagy through S6 Kinase Inhibition of the Insulin PathwayČlánek Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human DiseasesČlánek G×G×E for Lifespan in : Mitochondrial, Nuclear, and Dietary Interactions that Modify LongevityČlánek PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial MatrixČlánek Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus ConflictsČlánek The Impact of Population Demography and Selection on the Genetic Architecture of Complex TraitsČlánek Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar AcidificationČlánek The Case for Junk DNA
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