Functional and clinical impact of ARL15 in cutaneous melanoma aggressiveness

Detalhes bibliográficos
Autor(a) principal: Chaves, Pedro Nuno Gomes
Data de Publicação: 2023
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/59348
Resumo: Tese de mestrado, Biologia Molecular e Genética, 2023, Universidade de Lisboa, Faculdade de Ciências
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spelling Functional and clinical impact of ARL15 in cutaneous melanoma aggressivenesspequenas GTPases ADP ribosylation factor-likevia de sinalização MAPKvia de sinalização PI3Ksupressor de tumoresbiomarcadoresinvasãoTeses de mestrado - 2023Departamento de Biologia VegetalTese de mestrado, Biologia Molecular e Genética, 2023, Universidade de Lisboa, Faculdade de CiênciasCutaneous melanoma (CM) is the deadliest form of skin cancer despite accounting for less than 1% of cases. Although very treatable in early stages, advanced-stage CM has an abysmal survival rate mostly attributed to its high propensity for metastasis, making timely detection and adequate disease management critical. CM often presents with alterations in key cell signalling pathways such as in Ras/Raf/MEK/ERK (MAPK) and PI3K/Akt/mTOR (PI3K). In fact, more than 60% of CMs show aberrant activation of the MAPK pathway, frequently due to BRAF gene mutations. The downstream activation of these pathways is mainly facilitated by members of the molecular switch Ras superfamily of small GTPases, including ARL proteins, whose role in CM remains relatively unexplored. These pathways are essential for tumour progression as they are involved in membrane trafficking and cytoskeleton organization, critical mechanisms of cancer migration and invasion. Our research group found ARL GTPases to be aberrantly expressed in a previous in-silico analysis of CM data of The Cancer Genome Atlas network, with ARL15 being significantly downregulated compared to normal skin samples. ARL15 expression was also found to be correlated with a specific immune profile of CM patients and presented as an independent predictor of patient survival in the same study. We therefore sought to validate these findings in a cohort of IPOLFG patients, as well as investigate the role of ARL15 on the mechanisms behind CM aggressiveness using in vitro assays. Our results confirm that ARL15 is downregulated in CM and even more so in late-stage disease. However, we were unable to establish a correlation between ARL15 expression and patient prognosis in our samples thus far. Furthermore, we noted a statistically significant correlation between ARL15 expression and tumour-infiltrating Treg-like cells,suggesting a potential role for ARL15 in the modulation of the immune response in CM. However, a precise molecular characterisation of these cells must be performed in order to understand the mechanisms underlying this correlation. Notably, lentiviral knockdown of ARL15 in two distinct BRAF-mutant CM cell lines resulted in increased migratory and invasive capacities of cells, with no noticeable changes in cell viability. Taken together, these findings seem to suggest that ARL15 could be an important factor in the aggressiveness of CM, having a putative role as a tumour suppressor. While our study provides important insights into the potential role of ARL15 in CM, further research is needed to fully understand its mechanisms and effects on clinical outcomes. Nonetheless, the significance of this study could have broader implications for cancer research, as ARL proteins are dysregulated in many types of cancer and can therefore serve as potential biomarkers and therapeutic targets.Sousa, Marta Sofia PojoLopes, Carla A. M.Repositório da Universidade de LisboaChaves, Pedro Nuno Gomes2023-09-18T08:02:24Z202320232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10451/59348enginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:08:23Zoai:repositorio.ul.pt:10451/59348Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:09:16.851855Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Functional and clinical impact of ARL15 in cutaneous melanoma aggressiveness
title Functional and clinical impact of ARL15 in cutaneous melanoma aggressiveness
spellingShingle Functional and clinical impact of ARL15 in cutaneous melanoma aggressiveness
Chaves, Pedro Nuno Gomes
pequenas GTPases ADP ribosylation factor-like
via de sinalização MAPK
via de sinalização PI3K
supressor de tumores
biomarcadores
invasão
Teses de mestrado - 2023
Departamento de Biologia Vegetal
title_short Functional and clinical impact of ARL15 in cutaneous melanoma aggressiveness
title_full Functional and clinical impact of ARL15 in cutaneous melanoma aggressiveness
title_fullStr Functional and clinical impact of ARL15 in cutaneous melanoma aggressiveness
title_full_unstemmed Functional and clinical impact of ARL15 in cutaneous melanoma aggressiveness
title_sort Functional and clinical impact of ARL15 in cutaneous melanoma aggressiveness
author Chaves, Pedro Nuno Gomes
author_facet Chaves, Pedro Nuno Gomes
author_role author
dc.contributor.none.fl_str_mv Sousa, Marta Sofia Pojo
Lopes, Carla A. M.
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Chaves, Pedro Nuno Gomes
dc.subject.por.fl_str_mv pequenas GTPases ADP ribosylation factor-like
via de sinalização MAPK
via de sinalização PI3K
supressor de tumores
biomarcadores
invasão
Teses de mestrado - 2023
Departamento de Biologia Vegetal
topic pequenas GTPases ADP ribosylation factor-like
via de sinalização MAPK
via de sinalização PI3K
supressor de tumores
biomarcadores
invasão
Teses de mestrado - 2023
Departamento de Biologia Vegetal
description Tese de mestrado, Biologia Molecular e Genética, 2023, Universidade de Lisboa, Faculdade de Ciências
publishDate 2023
dc.date.none.fl_str_mv 2023-09-18T08:02:24Z
2023
2023
2023-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/59348
url http://hdl.handle.net/10451/59348
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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