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The Dark Side of Melanin Secretion in Cutaneous Melanoma Aggressiveness

2022-05-10Recensão Acesso aberto
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dc.contributor.authorCabaço, Luís C.
dc.contributor.authorCabaço, Luís C.
dc.contributor.authorTomás, Ana
dc.contributor.authorPojo, Marta
dc.contributor.authorBarral, Duarte C.
dc.contributor.authorC. Barral, Duarte
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.pblFrontiers Media
dc.date.accessioned2022-06-17T22:22:40Z
dc.date.available2022-06-17T22:22:40Z
dc.date.issued2022-05-10
dc.descriptionFunding Information: LC is funded by an FCT PhD fellowship (2020.08812.BD). AT is funded by an FCT PhD fellowship (2021.06204.BD). MP is funded by Liga Portuguesa Contra o Cancro – Núcleo Regional do Sul (LPCC-NRS). DB lab is supported by Fundação para a Ciência e a Tecnologia (FCT) through grant PTDC/BIA-CEL/29765/2017. This publication was funded by the iNOVA4Health - UIDB/04462/2020 and UIDP/04462/2020, a program financially supported by FCT/Ministério da Educação e Ciência through national funds and co-funded by FEDER under the PT2020 Partnership Agreement. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Publisher Copyright: Copyright © 2022 Cabaço, Tomás, Pojo and Barral.
dc.description.abstractSkin cancers are among the most common cancers worldwide and are increasingly prevalent. Cutaneous melanoma (CM) is characterized by the malignant transformation of melanocytes in the epidermis. Although CM shows lower incidence than other skin cancers, it is the most aggressive and responsible for the vast majority of skin cancer-related deaths. Indeed, 75% of patients present with invasive or metastatic tumors, even after surgical excision. In CM, the photoprotective pigment melanin, which is produced by melanocytes, plays a central role in the pathology of the disease. Melanin absorbs ultraviolet radiation and scavenges reactive oxygen/nitrogen species (ROS/RNS) resulting from the radiation exposure. However, the scavenged ROS/RNS modify melanin and lead to the induction of signature DNA damage in CM cells, namely cyclobutane pyrimidine dimers, which are known to promote CM immortalization and carcinogenesis. Despite triggering the malignant transformation of melanocytes and promoting initial tumor growth, the presence of melanin inside CM cells is described to negatively regulate their invasiveness by increasing cell stiffness and reducing elasticity. Emerging evidence also indicates that melanin secreted from CM cells is required for the immunomodulation of tumor microenvironment. Indeed, melanin transforms dermal fibroblasts in cancer-associated fibroblasts, suppresses the immune system and promotes tumor angiogenesis, thus sustaining CM progression and metastasis. Here, we review the current knowledge on the role of melanin secretion in CM aggressiveness and the molecular machinery involved, as well as the impact in tumor microenvironment and immune responses. A better understanding of this role and the molecular players involved could enable the modulation of melanin secretion to become a therapeutic strategy to impair CM invasion and metastasis and, hence, reduce the burden of CM-associated deaths.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent1149238
dc.identifier.doi10.3389/fonc.2022.887366
dc.identifier.issn2234-943X
dc.identifier.otherPURE: 44495145
dc.identifier.otherPURE UUID: 22a86929-e717-4904-8a93-e6ccf3a7353e
dc.identifier.otherScopus: 85130690166
dc.identifier.otherWOS: 000800350800001
dc.identifier.urihttp://hdl.handle.net/10362/140213
dc.identifier.urlhttps://www.scopus.com/pages/publications/85130690166
dc.language.isoeng
dc.peerreviewedyes
dc.subjectaggressiveness
dc.subjectcutaneous melanoma
dc.subjectimmunomodulation
dc.subjectmelanin
dc.subjectmelanin secretion
dc.subjectmelanogenesis
dc.subjectmicroenvironment
dc.subjectultraviolet radiation
dc.subjectOncology
dc.subjectCancer Research
dc.subjectSDG 3 - Good Health and Well-being
dc.titleThe Dark Side of Melanin Secretion in Cutaneous Melanoma Aggressivenessen
dc.typereview
degois.publication.titleFrontiers in Oncology
degois.publication.volume12
dspace.entity.typePublication
person.familyNameCabaço
person.familyNameBarral
person.givenNameLuís C.
person.givenNameDuarte
person.identifier1756697
person.identifier.ciencia-id6D1D-EC36-6BA3
person.identifier.ciencia-id8810-DEBC-025E
person.identifier.orcid0000-0003-0976-1781
person.identifier.orcid0000-0001-8867-2407
person.identifier.ridE-7548-2013
person.identifier.scopus-author-id57224771399
person.identifier.scopus-author-id6602513159
rcaap.rightsopenAccess
relation.isAuthorOfPublicationb545a125-c8cb-43af-a0c2-8b4dd1f7ee5f
relation.isAuthorOfPublicatione8205a0a-7fb2-450a-9917-417ec75d88b3
relation.isAuthorOfPublication.latestForDiscoveryb545a125-c8cb-43af-a0c2-8b4dd1f7ee5f

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