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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.1004321

Souhrn

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.


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Genetika Reprodukčná medicína

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PLOS Genetics


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