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

2019Journal article Restricted access
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dc.contributor.authorFaria, Márcia
dc.contributor.authorFélix, Daniela
dc.contributor.authorDomingues, Rita
dc.contributor.authorBugalho, Maria João
dc.contributor.authorMatos, Paulo
dc.contributor.authorSilva, Ana Luísa
dc.date.accessioned2020-01-09T12:03:51Z
dc.date.available2020-01-09T12:03:51Z
dc.date.issued2019
dc.description© 2019 Society for Endocrinology Printed in Great Britain. Published by Bioscientifica Ltd.pt_PT
dc.description.abstractThyroid 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.pt_PT
dc.description.sponsorshipThe 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJournal of Molecular Endocrinology (2019) 63, 309–320pt_PT
dc.identifier.doi10.1530/JME-19-0195pt_PT
dc.identifier.eissn1479-6813
dc.identifier.issn0952-5041
dc.identifier.urihttp://hdl.handle.net/10451/40754
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBioScientificapt_PT
dc.relationPTDC/BIAMOL/31787/2017pt_PT
dc.relationLimbertSPEDM/Genzyme-2015pt_PT
dc.relationTargeting Rac1-signaling to enhance iodide-related cancer therapy
dc.relation.publisherversionhttps://jme.bioscientifica.com/pt_PT
dc.subjectThyroid cancerpt_PT
dc.subjectSodium-iodide symporterpt_PT
dc.subjectRho GTPasespt_PT
dc.subjectSignalingpt_PT
dc.titleAntagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroidpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleTargeting Rac1-signaling to enhance iodide-related cancer therapy
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F114388%2F2016/PT
oaire.citation.endPage320pt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage309pt_PT
oaire.citation.titleJournal of Molecular Endocrinologypt_PT
oaire.citation.volume63pt_PT
person.familyNameFaria
person.familyNameCardoso Domingues
person.familyNameBugalho
person.familyNameSilva
person.givenNameMárcia
person.givenNameRita Sofia
person.givenNameMaria João
person.givenNameAna Luísa
person.identifier1596200
person.identifierF-5245-2012
person.identifier.ciencia-id0B12-EF2F-133D
person.identifier.ciencia-idD51C-30D5-71FC
person.identifier.ciencia-id0F14-CA4F-1358
person.identifier.ciencia-idD215-714A-CA06
person.identifier.orcid0000-0002-6601-1138
person.identifier.orcid0000-0001-7130-3795
person.identifier.orcid0000-0003-0357-7350
person.identifier.orcid0000-0002-9379-9696
person.identifier.orcid0000-0002-4839-8279
person.identifier.scopus-author-id35582359500
person.identifier.scopus-author-id7003265109
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication7991b5ef-7fad-4627-bc33-ca8c98fe85dc
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relation.isAuthorOfPublication093aa1a4-a2f3-469f-a4ce-c71cde6560ed
relation.isAuthorOfPublication.latestForDiscovery3284217a-2cd6-4fa6-85d9-ebf02f8509a6
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