Publicação
BRD9 status is a major contributor for cysteine metabolic remodeling through MST and EAAT3 modulation in malignant melanoma
| Resumo: | Cutaneous melanoma (CM) is the most aggressive skin cancer, showing globally increasing incidence. Hereditary CM accounts for a significant percentage (5-15 %) of all CM cases. However, most familial cases remain without a known genetic cause. Even though, BRD9 has been associated to CM as a susceptibility gene. The molecular events following BRD9 mutagenesis are still not completely understood. In this study, we disclosed BRD9 as a key regulator in cysteine metabolism and associated altered BRD9 to increased cell proliferation, migration and invasiveness, as well as to altered melanin levels, inducing higher susceptibility to melanomagenesis. It is evident that BRD9 WT and mutated BRD9 (c.183G>C) have a different impact on cysteine metabolism, respectively by inhibiting and activating MPST expression in the metastatic A375 cell line. The effect of the mutated BRD9 variant was more evident in A375 cells than in the less invasive WM115 line. Our data point out novel molecular and metabolic mechanisms dependent on BRD9 status that potentially account for the increased risk of developing CM and enhancing CM aggressiveness. Moreover, our findings emphasize the role of cysteine metabolism remodeling in melanoma progression and open new queues to follow to explore the role of BRD9 as a melanoma susceptibility or cancer-related gene. |
|---|---|
| Autores principais: | Hipólito, Ana |
| Outros Autores: | Xavier, Renato; Brito, Cheila; Tomás, Ana; Lemos, Isabel; Cabaço, Luís C.; Cabaço, Luís C.; Silva, Fernanda; Oliva, Abel; Barral, Duarte C.; C. Barral, Duarte; Vicente, João B.; Gonçalves, Luís G.; Pojo, Marta; Serpa, Jacinta; Serpa, Jacinta |
| Assunto: | BRD9 Cutaneous melanoma Cysteine metabolism Metabolic remodeling Molecular Medicine Molecular Biology SDG 3 - Good Health and Well-being |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| _version_ | 1868982352382787584 |
|---|---|
| author | Hipólito, Ana |
| author2 | Xavier, Renato Brito, Cheila Tomás, Ana Lemos, Isabel Cabaço, Luís C. Cabaço, Luís C. Silva, Fernanda Oliva, Abel Barral, Duarte C. C. Barral, Duarte Vicente, João B. Gonçalves, Luís G. Pojo, Marta Serpa, Jacinta Serpa, Jacinta |
| author2_role | author author author author author author author author author author author author author author author |
| author_facet | Hipólito, Ana Xavier, Renato Brito, Cheila Tomás, Ana Lemos, Isabel Cabaço, Luís C. Cabaço, Luís C. Silva, Fernanda Oliva, Abel Barral, Duarte C. C. Barral, Duarte Vicente, João B. Gonçalves, Luís G. Pojo, Marta Serpa, Jacinta Serpa, Jacinta |
| author_role | author |
| contributor_name_str_mv | NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) iNOVA4Health - pólo NMS Instituto de Tecnologia Química e Biológica António Xavier (ITQB) Elsevier RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Hipólito, Ana\"},{\"Person.name\":\"Xavier, Renato\"},{\"Person.name\":\"Brito, Cheila\"},{\"Person.name\":\"Tomás, Ana\"},{\"Person.name\":\"Lemos, Isabel\"},{\"Person.name\":\"Cabaço, Luís C.\"},{\"Person.name\":\"Cabaço, Luís C.\",\"Person.identifier.orcid\":\"0000-0003-0976-1781\"},{\"Person.name\":\"Silva, Fernanda\"},{\"Person.name\":\"Oliva, Abel\"},{\"Person.name\":\"Barral, Duarte C.\"},{\"Person.name\":\"C. Barral, Duarte\",\"Person.identifier.orcid\":\"0000-0001-8867-2407\"},{\"Person.name\":\"Vicente, João B.\"},{\"Person.name\":\"Gonçalves, Luís G.\"},{\"Person.name\":\"Pojo, Marta\"},{\"Person.name\":\"Serpa, Jacinta\"},{\"Person.name\":\"Serpa, Jacinta\",\"Person.identifier.orcid\":\"0000-0002-1548-5907\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) iNOVA4Health - pólo NMS Instituto de Tecnologia Química e Biológica António Xavier (ITQB) Elsevier RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Hipólito, Ana Xavier, Renato Brito, Cheila Tomás, Ana Lemos, Isabel Cabaço, Luís C. Cabaço, Luís C. Silva, Fernanda Oliva, Abel Barral, Duarte C. C. Barral, Duarte Vicente, João B. Gonçalves, Luís G. Pojo, Marta Serpa, Jacinta Serpa, Jacinta |
| datacite.date.Accepted.fl_str_mv | 2024-02-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2024-01-17T22:27:14Z |
| datacite.date.embargoed.fl_str_mv | 2024-01-17T22:27:14Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | BRD9 Cutaneous melanoma Cysteine metabolism Metabolic remodeling Molecular Medicine Molecular Biology SDG 3 - Good Health and Well-being |
| datacite.titles.title.fl_str_mv | BRD9 status is a major contributor for cysteine metabolic remodeling through MST and EAAT3 modulation in malignant melanoma |
| dc.contributor.none.fl_str_mv | NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) iNOVA4Health - pólo NMS Instituto de Tecnologia Química e Biológica António Xavier (ITQB) Elsevier RUN |
| dc.creator.none.fl_str_mv | Hipólito, Ana Xavier, Renato Brito, Cheila Tomás, Ana Lemos, Isabel Cabaço, Luís C. Cabaço, Luís C. Silva, Fernanda Oliva, Abel Barral, Duarte C. C. Barral, Duarte Vicente, João B. Gonçalves, Luís G. Pojo, Marta Serpa, Jacinta Serpa, Jacinta |
| dc.date.Accepted.fl_str_mv | 2024-02-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2024-01-17T22:27:14Z |
| dc.date.embargoed.fl_str_mv | 2024-01-17T22:27:14Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/162409 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | BRD9 Cutaneous melanoma Cysteine metabolism Metabolic remodeling Molecular Medicine Molecular Biology SDG 3 - Good Health and Well-being |
| dc.title.fl_str_mv | BRD9 status is a major contributor for cysteine metabolic remodeling through MST and EAAT3 modulation in malignant melanoma |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Cutaneous melanoma (CM) is the most aggressive skin cancer, showing globally increasing incidence. Hereditary CM accounts for a significant percentage (5-15 %) of all CM cases. However, most familial cases remain without a known genetic cause. Even though, BRD9 has been associated to CM as a susceptibility gene. The molecular events following BRD9 mutagenesis are still not completely understood. In this study, we disclosed BRD9 as a key regulator in cysteine metabolism and associated altered BRD9 to increased cell proliferation, migration and invasiveness, as well as to altered melanin levels, inducing higher susceptibility to melanomagenesis. It is evident that BRD9 WT and mutated BRD9 (c.183G>C) have a different impact on cysteine metabolism, respectively by inhibiting and activating MPST expression in the metastatic A375 cell line. The effect of the mutated BRD9 variant was more evident in A375 cells than in the less invasive WM115 line. Our data point out novel molecular and metabolic mechanisms dependent on BRD9 status that potentially account for the increased risk of developing CM and enhancing CM aggressiveness. Moreover, our findings emphasize the role of cysteine metabolism remodeling in melanoma progression and open new queues to follow to explore the role of BRD9 as a melanoma susceptibility or cancer-related gene. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/e50c3de5-618a-498c-bb63-20c76d568c68/download |
| id | run_00d3db0b7409db2de8ce04c4bc7dcfec |
| identifier.url.fl_str_mv | http://hdl.handle.net/10362/162409 |
| inst_facet_str | urn:organizationAcronym:unl{{{_:::_}}}Universidade Nova de Lisboa |
| instacron_str | unl |
| institution | Universidade Nova de Lisboa |
| instname_str | Universidade Nova de Lisboa |
| language | eng |
| network_acronym_str | run |
| network_name_str | Repositório Institucional da UNL |
| oai_identifier_str | oai:run.unl.pt:10362/162409 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Hipólito, Ana Xavier, Renato Brito, Cheila Tomás, Ana Lemos, Isabel Cabaço, Luís C. Cabaço, Luís C. Cabaço, Luís C. https://www.ciencia-id.pt/6D1D-EC36-6BA3 6D1D-EC36-6BA3 http://orcid.org/0000-0003-0976-1781 0000-0003-0976-1781 Silva, Fernanda Oliva, Abel Barral, Duarte C. C. Barral, Duarte C. Barral, Duarte https://www.ciencia-id.pt/8810-DEBC-025E 8810-DEBC-025E http://orcid.org/0000-0001-8867-2407 0000-0001-8867-2407 Vicente, João B. Gonçalves, Luís G. Pojo, Marta Serpa, Jacinta Serpa, Jacinta Serpa, Jacinta https://www.ciencia-id.pt/2610-7C0D-38F2 2610-7C0D-38F2 http://orcid.org/0000-0002-1548-5907 0000-0002-1548-5907 |
| publishDate | 2024 |
| repo_facet_str | urn:repositoryAcronym:run{{{_:::_}}}Repositório Institucional da UNL |
| reponame_str | Repositório Institucional da UNL |
| repository_id_str | urn:repositoryAcronym:run |
| service_str_mv | urn:repositoryAcronym:run |
| spelling | engenCutaneous melanoma (CM) is the most aggressive skin cancer, showing globally increasing incidence. Hereditary CM accounts for a significant percentage (5-15 %) of all CM cases. However, most familial cases remain without a known genetic cause. Even though, BRD9 has been associated to CM as a susceptibility gene. The molecular events following BRD9 mutagenesis are still not completely understood. In this study, we disclosed BRD9 as a key regulator in cysteine metabolism and associated altered BRD9 to increased cell proliferation, migration and invasiveness, as well as to altered melanin levels, inducing higher susceptibility to melanomagenesis. It is evident that BRD9 WT and mutated BRD9 (c.183G>C) have a different impact on cysteine metabolism, respectively by inhibiting and activating MPST expression in the metastatic A375 cell line. The effect of the mutated BRD9 variant was more evident in A375 cells than in the less invasive WM115 line. Our data point out novel molecular and metabolic mechanisms dependent on BRD9 status that potentially account for the increased risk of developing CM and enhancing CM aggressiveness. Moreover, our findings emphasize the role of cysteine metabolism remodeling in melanoma progression and open new queues to follow to explore the role of BRD9 as a melanoma susceptibility or cancer-related gene.application/pdfenBRD9 status is a major contributor for cysteine metabolic remodeling through MST and EAAT3 modulation in malignant melanomaHipólito, AnaXavier, RenatoBrito, CheilaTomás, AnaLemos, IsabelCabaço, Luís C.PersonalCabaço, Luís C.DSpacehttp://dspace.org/items/b545a125-c8cb-43af-a0c2-8b4dd1f7ee5fDSpacehttp://dspace.org/items/b545a125-c8cb-43af-a0c2-8b4dd1f7ee5fCabaçoLuís C.Ciência IDhttps://www.ciencia-id.pt6D1D-EC36-6BA3ORCIDhttp://orcid.org0000-0003-0976-1781Scopus Author IDhttps://www.scopus.com57224771399Silva, FernandaOliva, AbelBarral, Duarte C.PersonalC. Barral, DuarteDSpacehttp://dspace.org/items/e8205a0a-7fb2-450a-9917-417ec75d88b3DSpacehttp://dspace.org/items/e8205a0a-7fb2-450a-9917-417ec75d88b3BarralDuarteCiência IDhttps://www.ciencia-id.pt8810-DEBC-025EORCIDhttp://orcid.org0000-0001-8867-2407Researcher IDhttps://www.researcherid.comE-7548-2013Scopus Author IDhttps://www.scopus.com6602513159Scopus Author IDhttps://www.scopus.com6602513159Vicente, João B.Gonçalves, Luís G.Pojo, MartaSerpa, JacintaPersonalSerpa, JacintaDSpacehttp://dspace.org/items/5f6eaca2-f01f-4894-8da2-688671913214DSpacehttp://dspace.org/items/5f6eaca2-f01f-4894-8da2-688671913214SerpaJacintaCiência IDhttps://www.ciencia-id.pt2610-7C0D-38F2ORCIDhttp://orcid.org0000-0002-1548-5907Researcher IDhttps://www.researcherid.comO-8942-2014Scopus Author IDhttps://www.scopus.com6601922586Scopus Author IDhttps://www.scopus.com56623388500Scopus Author IDhttps://www.scopus.com56623388500NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)iNOVA4Health - pólo NMSInstituto de Tecnologia Química e Biológica António Xavier (ITQB)ElsevierHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf1879-260XURNIsPartOfPURE: 81028392URNIsPartOfPURE UUID: 840b30bb-52c6-42da-96cc-1c144261dd44URNIsPartOfScopus: 85181396377URNIsPartOfPubMed: 38070581URNIsPartOfORCID: 0000-0001-8867-2407/work/149584570URNIsPartOfORCID: /0000-0001-8867-2407/work/151365894URNIsPartOfORCID: /0000-0001-5683-3552/work/151405763URNIsPartOfORCID: /0000-0002-1548-5907/work/151423015URNIsPartOfWOS: 001137400700001DOIIsPartOf10.1016/j.bbadis.2023.1669832024-01-17T22:27:14Z2024-02-012024-02-01T00:00:00ZHandlehttp://hdl.handle.net/10362/162409http://purl.org/coar/access_right/c_abf2open accessBRD9Cutaneous melanomaCysteine metabolismMetabolic remodelingMolecular MedicineMolecular BiologySDG 3 - Good Health and Well-being11992259 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/e50c3de5-618a-498c-bb63-20c76d568c68/download |
| spellingShingle | BRD9 status is a major contributor for cysteine metabolic remodeling through MST and EAAT3 modulation in malignant melanoma Hipólito, Ana BRD9 Cutaneous melanoma Cysteine metabolism Metabolic remodeling Molecular Medicine Molecular Biology SDG 3 - Good Health and Well-being |
| status | SINGLETON |
| subject.fl_str_mv | BRD9 Cutaneous melanoma Cysteine metabolism Metabolic remodeling Molecular Medicine Molecular Biology SDG 3 - Good Health and Well-being |
| title | BRD9 status is a major contributor for cysteine metabolic remodeling through MST and EAAT3 modulation in malignant melanoma |
| title_full | BRD9 status is a major contributor for cysteine metabolic remodeling through MST and EAAT3 modulation in malignant melanoma |
| title_fullStr | BRD9 status is a major contributor for cysteine metabolic remodeling through MST and EAAT3 modulation in malignant melanoma |
| title_full_unstemmed | BRD9 status is a major contributor for cysteine metabolic remodeling through MST and EAAT3 modulation in malignant melanoma |
| title_short | BRD9 status is a major contributor for cysteine metabolic remodeling through MST and EAAT3 modulation in malignant melanoma |
| title_sort | BRD9 status is a major contributor for cysteine metabolic remodeling through MST and EAAT3 modulation in malignant melanoma |
| topic | BRD9 Cutaneous melanoma Cysteine metabolism Metabolic remodeling Molecular Medicine Molecular Biology SDG 3 - Good Health and Well-being |
| topic_facet | BRD9 Cutaneous melanoma Cysteine metabolism Metabolic remodeling Molecular Medicine Molecular Biology SDG 3 - Good Health and Well-being |
| url | http://hdl.handle.net/10362/162409 |
| visible | 1 |