{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T23:29:23Z","timestamp":1767828563636,"version":"3.49.0"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T00:00:00Z","timestamp":1412899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Medical Faculty of the RWTH Aachen University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Retinoids such as all\u2010<jats:italic>trans<\/jats:italic> retinoic acid (<jats:styled-content style=\"fixed-case\">ATRA<\/jats:styled-content>) influence cell growth, differentiation and apoptosis and may play decisive roles in tumor development and progression. An essential retinoid\u2010metabolizing enzyme known as lecithin retinol acyltransferase (<jats:styled-content style=\"fixed-case\">LRAT<\/jats:styled-content>) is expressed in melanoma cells but not in melanocytes catalysing the esterification of all\u2010<jats:italic>trans<\/jats:italic> retinol (<jats:styled-content style=\"fixed-case\">ATR<\/jats:styled-content>ol). In this study, we show that a stable <jats:styled-content style=\"fixed-case\">LRAT<\/jats:styled-content> knockdown (<jats:styled-content style=\"fixed-case\">KD<\/jats:styled-content>) in the human melanoma cell line SkMel23 leads to significantly increased levels of the substrate <jats:styled-content style=\"fixed-case\">ATR<\/jats:styled-content>ol and biologically active <jats:styled-content style=\"fixed-case\">ATRA<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">LRAT KD<\/jats:styled-content> restored cellular sensitivity to retinoids analysed in cell culture assays and melanoma 3D skin models. Furthermore, <jats:styled-content style=\"fixed-case\">ATRA<\/jats:styled-content>\u2010induced gene regulatory mechanisms drive depletion of added <jats:styled-content style=\"fixed-case\">ATR<\/jats:styled-content>ol in <jats:styled-content style=\"fixed-case\">LRAT KD<\/jats:styled-content> cells. <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> analysis revealed a significant upregulation of retinoid\u2010regulated genes such as <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>26A1 and <jats:styled-content style=\"fixed-case\">STRA<\/jats:styled-content>6 in <jats:styled-content style=\"fixed-case\">LRAT KD<\/jats:styled-content> cells, suggesting their possible involvement in mediating retinoid resistance in melanoma cells. In conclusion, <jats:styled-content style=\"fixed-case\">LRAT<\/jats:styled-content> seems to be important for melanoma progression. We propose that reduction in <jats:styled-content style=\"fixed-case\">ATR<\/jats:styled-content>ol levels in melanoma cells by <jats:styled-content style=\"fixed-case\">LRAT<\/jats:styled-content> leads to a disturbance in cellular retinoid level. Balanced <jats:styled-content style=\"fixed-case\">LRAT<\/jats:styled-content> expression and activity may provide protection against melanoma development and progression. Pharmacological inhibition of <jats:styled-content style=\"fixed-case\">LRAT<\/jats:styled-content> activity could be a promising strategy for overcoming retinoid insensitivity in human melanoma cells.<\/jats:p>","DOI":"10.1111\/exd.12548","type":"journal-article","created":{"date-parts":[[2014,9,18]],"date-time":"2014-09-18T15:57:09Z","timestamp":1411055829000},"page":"832-837","source":"Crossref","is-referenced-by-count":6,"title":["Knockdown of lecithin retinol acyltransferase increases all\u2010<i>trans<\/i> retinoic acid levels and restores retinoid sensitivity in malignant melanoma cells"],"prefix":"10.1111","volume":"23","author":[{"given":"Philipp M.","family":"Amann","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergology RWTH Aachen University Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Czaja","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology RWTH 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