Antagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroid

Detalhes bibliográficos
Autor(a) principal: Faria, Márcia
Data de Publicação: 2019
Outros Autores: Félix, Daniela, Domingues, Rita, Bugalho, Maria João, Matos, Paulo, Silva, Ana Luísa
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/6471
Resumo: Supplementary data: Figure 1 supplemental: NIS and RAC1b expression data retrieved from TCGA database. NIS and RAC1b isoform expression data was collected from The Cancer Genome Atlas (TCGA) project [Thyroid Carcinoma (THCA) project] using the TSVdb tool (Sun et al. 2018). NIS and RAC1b RNA-Seq data was retrieved in the RSEM format (Li & Dewey 2011). Results are depicted as Tukey’s boxplots of the LOG2 RSEM values of each sample, comparing primary PTC (n=501) and normal solid thyroid tissue (n=59) data sets. The existence of significant differences between the two datasets was evaluated using a two-tailed Mann-Whitney’s u-test, assuming a significance level of α=0.05.
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spelling Antagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroidSodium Iodide SymporterRAC1bThyroid CancerVias de Transdução de Sinal e Patologias AssociadasSupplementary data: Figure 1 supplemental: NIS and RAC1b expression data retrieved from TCGA database. NIS and RAC1b isoform expression data was collected from The Cancer Genome Atlas (TCGA) project [Thyroid Carcinoma (THCA) project] using the TSVdb tool (Sun et al. 2018). NIS and RAC1b RNA-Seq data was retrieved in the RSEM format (Li & Dewey 2011). Results are depicted as Tukey’s boxplots of the LOG2 RSEM values of each sample, comparing primary PTC (n=501) and normal solid thyroid tissue (n=59) data sets. The existence of significant differences between the two datasets was evaluated using a two-tailed Mann-Whitney’s u-test, assuming a significance level of α=0.05.Thyroid cancer (TC) is the most common endocrine malignancy. The Sodium Iodide Symporter (NIS), responsible for active transport of iodide into thyroid cells, allows the use of radioactive iodine (RAI) as the systemic treatment of choice for TC metastatic disease. Still, patients with advanced forms of TC often lose the ability to respond to RAI therapy, which results in worse survival rates. We have shown that the overexpression of RAC1b, a tumor-related RAC1 splice variant, is associated with less favorable clinical outcomes in differentiated TCs derived from the follicular epithelial (DTCs). RAC1b overexpression is also significantly associated with the presence of MAPK-activating BRAFV600E mutation, which has been previously implicated in the loss of NIS expression. Here, we show that increased RAC1b levels are associated with NIS downregulation in DTCs and demonstrate that ectopic overexpression of RAC1b in non-transformed thyroid cells is sufficient to decrease TSH-induced NIS expression, antagonizing the positive effect of the canonically spliced RAC1 GTPase. Moreover, we clearly document for the first time in thyroid cells that both NIS expression and iodide uptake are hampered by RAC1 inhibition, highlighting the role of RAC1 in promoting TSH-induced NIS expression. Our findings support a role for RAC1 and RAC1b signaling in the regulation of NIS expression in thyroid cells and suggest that RAC1b in cooperation with other cancer-associated signaling cues may be implicated in the response of DTCs to RAI therapy.The authors acknowledge the support from grants PTDC/BIAMOL/31787/2017 (from FTC, Portugal) and LimbertSPEDM/Genzyme-2015 (from SPEDM/Genzyme, Portugal). M F is recipient of FCT fellowship PD/BD/114388/2016.BioScientifica/ Society for EndocrinologyRepositório Científico do Instituto Nacional de SaúdeFaria, MárciaFélix, DanielaDomingues, RitaBugalho, Maria JoãoMatos, PauloSilva, Ana Luísa2020-04-21T16:19:27Z2019-112019-11-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6471engJ Mol Endocrinol. 2019 Nov;63(4):309-320. doi: 10.1530/JME-19-019510.1530/JME-19-0195info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:41:31Zoai:repositorio.insa.pt:10400.18/6471Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:41:15.463019Repositório 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 Antagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroid
title Antagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroid
spellingShingle Antagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroid
Faria, Márcia
Sodium Iodide Symporter
RAC1b
Thyroid Cancer
Vias de Transdução de Sinal e Patologias Associadas
title_short Antagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroid
title_full Antagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroid
title_fullStr Antagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroid
title_full_unstemmed Antagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroid
title_sort Antagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroid
author Faria, Márcia
author_facet Faria, Márcia
Félix, Daniela
Domingues, Rita
Bugalho, Maria João
Matos, Paulo
Silva, Ana Luísa
author_role author
author2 Félix, Daniela
Domingues, Rita
Bugalho, Maria João
Matos, Paulo
Silva, Ana Luísa
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Faria, Márcia
Félix, Daniela
Domingues, Rita
Bugalho, Maria João
Matos, Paulo
Silva, Ana Luísa
dc.subject.por.fl_str_mv Sodium Iodide Symporter
RAC1b
Thyroid Cancer
Vias de Transdução de Sinal e Patologias Associadas
topic Sodium Iodide Symporter
RAC1b
Thyroid Cancer
Vias de Transdução de Sinal e Patologias Associadas
description Supplementary data: Figure 1 supplemental: NIS and RAC1b expression data retrieved from TCGA database. NIS and RAC1b isoform expression data was collected from The Cancer Genome Atlas (TCGA) project [Thyroid Carcinoma (THCA) project] using the TSVdb tool (Sun et al. 2018). NIS and RAC1b RNA-Seq data was retrieved in the RSEM format (Li & Dewey 2011). Results are depicted as Tukey’s boxplots of the LOG2 RSEM values of each sample, comparing primary PTC (n=501) and normal solid thyroid tissue (n=59) data sets. The existence of significant differences between the two datasets was evaluated using a two-tailed Mann-Whitney’s u-test, assuming a significance level of α=0.05.
publishDate 2019
dc.date.none.fl_str_mv 2019-11
2019-11-01T00:00:00Z
2020-04-21T16:19:27Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/6471
url http://hdl.handle.net/10400.18/6471
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv J Mol Endocrinol. 2019 Nov;63(4):309-320. doi: 10.1530/JME-19-0195
10.1530/JME-19-0195
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioScientifica/ Society for Endocrinology
publisher.none.fl_str_mv BioScientifica/ Society for Endocrinology
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
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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
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