Alpha-melanocyte stimulating hormone (α-MSH): biology, clinical relevance and implication in melanoma

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Alpha-melanocyte stimulating hormone (α-MSH) and its receptor, melanocortin 1 receptor (MC1R), have been proposed as potential target for anti-cancer strategies in melanoma research, due to their tissue specific expression and involvement in melanocyte homeostasis. However, their role in prevention and treatment of melanoma is still debated and controversial. Although a large body of evidence supports α-MSH in preventing melanoma development, some preclinical findings suggest that the α-MSH downstream signalling may promote immune escape and cancer resistance to therapy. Additionally, in metastatic melanoma both MC1R and α-MSH have been reported to be overexpressed at levels much higher than normal cells. Furthermore, targeted therapy (e.g. BRAF inhibition in BRAF ^V600E mutant tumours) has been shown to enhance this phenomenon. Collectively, these data suggest that targeting MC1R could serve as an approach in the treatment of metastatic melanoma. In this review, we explore the molecular biology of α-MSH with particular emphasis into its tumor-related properties, whilst elaborating the experimental evidence currently available regarding the interplay between α-MSH/MC1R axis, melanoma and antitumor strategies.

Related collections

Most cited references 96

Record: found
Abstract: found
Article: found

Is Open Access

UV Radiation and the Skin

John D'Orazio, Stuart Jarrett, Alexandra Amaro-Ortiz … (2013)

UV radiation (UV) is classified as a “complete carcinogen” because it is both a mutagen and a non-specific damaging agent and has properties of both a tumor initiator and a tumor promoter. In environmental abundance, UV is the most important modifiable risk factor for skin cancer and many other environmentally-influenced skin disorders. However, UV also benefits human health by mediating natural synthesis of vitamin D and endorphins in the skin, therefore UV has complex and mixed effects on human health. Nonetheless, excessive exposure to UV carries profound health risks, including atrophy, pigmentary changes, wrinkling and malignancy. UV is epidemiologically and molecularly linked to the three most common types of skin cancer, basal cell carcinoma, squamous cell carcinoma and malignant melanoma, which together affect more than a million Americans annually. Genetic factors also influence risk of UV-mediated skin disease. Polymorphisms of the melanocortin 1 receptor (MC1R) gene, in particular, correlate with fairness of skin, UV sensitivity, and enhanced cancer risk. We are interested in developing UV-protective approaches based on a detailed understanding of molecular events that occur after UV exposure, focusing particularly on epidermal melanization and the role of the MC1R in genome maintenance.

0 comments Cited 372 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

A landscape of driver mutations in melanoma.

Eran Hodis, Ian R. Watson, Gregory V. Kryukov … (2012)

Despite recent insights into melanoma genetics, systematic surveys for driver mutations are challenged by an abundance of passenger mutations caused by carcinogenic UV light exposure. We developed a permutation-based framework to address this challenge, employing mutation data from intronic sequences to control for passenger mutational load on a per gene basis. Analysis of large-scale melanoma exome data by this approach discovered six novel melanoma genes (PPP6C, RAC1, SNX31, TACC1, STK19, and ARID2), three of which-RAC1, PPP6C, and STK19-harbored recurrent and potentially targetable mutations. Integration with chromosomal copy number data contextualized the landscape of driver mutations, providing oncogenic insights in BRAF- and NRAS-driven melanoma as well as those without known NRAS/BRAF mutations. The landscape also clarified a mutational basis for RB and p53 pathway deregulation in this malignancy. Finally, the spectrum of driver mutations provided unequivocal genomic evidence for a direct mutagenic role of UV light in melanoma pathogenesis. Copyright © 2012 Elsevier Inc. All rights reserved.

0 comments Cited 364 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans.

P Valverde, E. Healy, I Jackson … (1995)

Melanin pigmentation protects the skin from the damaging effects of ultraviolet radiation (UVR). There are two types of melanin, the red phaeomelanin and the black eumelanin, both of which are present in human skin. Eumelanin is photoprotective whereas phaeomelanin, because of its potential to generate free radicals in response to UVR, may contribute to UV-induced skin damage. Individuals with red hair have a predominance of phaeomelain in hair and skin and/or a reduced ability to produce eumelanin, which may explain why they fail to tan and are at risk from UVR. In mammals the relative proportions of phaeomelanin and eumelanin are regulated by melanocyte stimulating hormone (MSH), which acts via its receptor (MC1R), on melanocytes, to increase the synthesis of eumelanin and the product of the agouti locus which antagonises this action. In mice, mutations at either the MC1R gene or agouti affect the pattern of melanogenesis resulting in changes in coat colour. We now report the presence of MC1R gene sequence variants in humans. These were found in over 80% of individuals with red hair and/or fair skin that tans poorly but in fewer than 20% of individuals with brown or black hair and in less than 4% of those who showed a good tanning response. Our findings suggest that in humans, as in other mammals, the MC1R is a control point in the regulation of pigmentation phenotype and, more importantly, that variations in this protein are associated with a poor tanning response.

0 comments Cited 202 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Luigi Dall’Olmo:

ORCID: http://orcid.org/0000-0003-1564-2594

luigi.dallolmo@unipd.it

Journal

Journal ID (nlm-ta): J Transl Med

Journal ID (iso-abbrev): J Transl Med

Title: Journal of Translational Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1479-5876

Publication date (Electronic): 22 August 2023

Publication date PMC-release: 22 August 2023

Publication date Collection: 2023

Volume: 21

Electronic Location Identifier: 562

Affiliations

[1 ]GRID grid.5608.b, ISNI 0000 0004 1757 3470, Department of Surgical Oncological and Gastroenterological Sciences, , Padua University, ; Via Giustiniani 2, 35128 Padua, Italy

[2 ]GRID grid.419546.b, ISNI 0000 0004 1808 1697, Istituto Oncologico Veneto IOV-IRCCS, ; 35128 Padua, Italy

[3 ]GRID grid.418879.b, ISNI 0000 0004 1758 9800, Neuroscience Institute, National Research Council of Italy (CNR), ; 35121 Padua, Italy

[4 ]GRID grid.428736.c, Veneto Institute of Molecular Medicine VIMM, Foundation for Advanced Biomedical Research, ; 35129 Padua, Italy

Author information

Luigi Dall’Olmo http://orcid.org/0000-0003-1564-2594

Article

Publisher ID: 4405

DOI: 10.1186/s12967-023-04405-y

PMC ID: 10463388

PubMed ID: 37608347

SO-VID: 2f5d77f4-c31d-4975-95d9-7917dd8eb66c

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 3 May 2023

Date accepted : 1 August 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100009414, Istituto Oncologico Veneto;

Award ID: “5x1000” IOV grant

Award Recipient : Nicole Papa

Funded by: Università degli Studi di Padova

Open Access :

Open access funding provided by Università degli Studi di Padova within the CRUI-CARE Agreement.

Custom metadata

ScienceOpen disciplines: Medicine

Keywords: melanoma,α-msh,mc1r,melanoma resistance,anticancer strategies

Data availability:

ScienceOpen disciplines: Medicine

Keywords: melanoma, α-msh, mc1r, melanoma resistance, anticancer strategies

Comments

Comment on this article

scite_

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

Cited by 6

See all cited by

Most referenced authors 1,297

See all reference authors

Alpha-melanocyte stimulating hormone (α-MSH): biology, clinical relevance and implication in melanoma

Read this article at

Abstract

Related collections

Vascular Biology

Most cited references 96

UV Radiation and the Skin

A landscape of driver mutations in melanoma.

Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans.

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 563

Cited by 6

Most referenced authors 1,297