Targeting GPCRs and Their Signaling as a Therapeutic Option in Melanoma
Open accessPublished version of a preprint
Abstract
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.
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- Authors
- Raymond, J. H., Aktary, Z., Larue, L., & Delmas, V.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Larue, Lionel
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2022-01-29
- Volume
- 14
- Issue
- 3
- Pages
- 706
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC8833576
- OpenAlex
- W4212959360
- Cited by
- 20
- References
- 15
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 3
- FWCI
- 0.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- Preprints.org (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fondation pour la Recherche Médicale (-)
- Institut Carnot Curie (-)
- French National Centre for Scientific Research (-)
- Inserm (-)
- Gefluc Ile-de-France (-)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- G protein-coupled receptors, melanoma, melanomagenesis, melanocyte homeostasis, pigmentation, G protein signaling, ultraviolet radiation, preclinical models
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