{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:02:56Z","timestamp":1791327776972,"version":"4.3.1"},"reference-count":366,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institut Carnot Curie","award":["-"],"award-info":[{"award-number":["-"]}]},{"DOI":"10.13039\/501100004794","name":"French National Centre for Scientific Research","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Inserm","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gefluc Ile-de-France","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>G-protein-coupled receptors (GPCRs) serve prominent roles in melanocyte lineage physiology, with an impact at all stages of development, as well as on mature melanocyte functions. GPCR ligands are present in the skin and regulate melanocyte homeostasis, including pigmentation. The role of GPCRs in the regulation of pigmentation and, consequently, protection against external aggression, such as ultraviolet radiation, has long been established. However, evidence of new functions of GPCRs directly in melanomagenesis has been highlighted in recent years. GPCRs are coupled, through their intracellular domains, to heterotrimeric G-proteins, which induce cellular signaling through various pathways. Such signaling modulates numerous essential cellular processes that occur during melanomagenesis, including proliferation and migration. GPCR-associated signaling in melanoma can be activated by the binding of paracrine factors to their receptors or directly by activating mutations. In this review, we present melanoma-associated alterations of GPCRs and their downstream signaling and discuss the various preclinical models used to evaluate new therapeutic approaches against GPCR activity in melanoma. Recent striking advances in our understanding of the structure, function, and regulation of GPCRs will undoubtedly broaden melanoma treatment options in the future.<\/jats:p>","DOI":"10.3390\/cancers14030706","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T23:02:06Z","timestamp":1643497326000},"page":"706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Targeting GPCRs and Their Signaling as a Therapeutic Option in Melanoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8712-895X","authenticated-orcid":false,"given":"J\u00e9r\u00e9my H.","family":"Raymond","sequence":"first","affiliation":[{"name":"Institut Curie, Universit\u00e9 PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes, 91400 Orsay, France"},{"name":"Universit\u00e9 Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zackie","family":"Aktary","sequence":"additional","affiliation":[{"name":"Institut Curie, Universit\u00e9 PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes, 91400 Orsay, France"},{"name":"Universit\u00e9 Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Larue","sequence":"additional","affiliation":[{"name":"Institut Curie, Universit\u00e9 PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes, 91400 Orsay, France"},{"name":"Universit\u00e9 Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7368-3664","authenticated-orcid":false,"given":"V\u00e9ronique","family":"Delmas","sequence":"additional","affiliation":[{"name":"Institut Curie, Universit\u00e9 PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes, 91400 Orsay, France"},{"name":"Universit\u00e9 Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.tips.2019.04.001","article-title":"GPCRomics: An Approach to Discover GPCR Drug Targets","volume":"40","author":"Insel","year":"2019","journal-title":"Trends Pharmacol. 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