Publication
Adherens Junction Integrity Is a Critical Determinant of Sodium Iodide Symporter Residency at the Plasma Membrane of Thyroid Cells
| dc.contributor.author | Faria, Márcia | |
| dc.contributor.author | Vareda, José | |
| dc.contributor.author | Miranda, Micaella | |
| dc.contributor.author | Bugalho, Maria João | |
| dc.contributor.author | Silva, Ana Luísa | |
| dc.contributor.author | Matos, Paulo | |
| dc.date.accessioned | 2023-01-10T14:11:41Z | |
| dc.date.available | 2023-01-10T14:11:41Z | |
| dc.date.issued | 2022-10-31 | |
| dc.description | This article belongs to the Special Issue Thyroid Carcinoma | pt_PT |
| dc.description.abstract | While most cases of differentiated thyroid carcinoma (DTC) are associated with a good prognosis, a significant number progress to advanced disease exhibiting aggressive clinical characteristics and often becoming refractory to radioactive iodine (RAI) treatment, the current gold-standard therapeutic option for metastatic disease. RAI-refractoriness is caused by defective functional expression of the sodium-iodide symporter (NIS), which is responsible for the active transport of iodide across the plasma membrane (PM) into thyroid follicles. NIS deficiency in these tumors often reflects a transcriptional impairment, but also its defective targeting and retention at the cells’ PM. Using proteomics, we previously characterized an intracellular signaling pathway derived from SRC kinase that acts through the small GTPase RAC1 to recruit and bind the actin-anchoring adaptor EZRIN to NIS, regulating its retention at the PM of both non-transformed and cancer thyroid cells. Here, we describe how by reanalyzing the proteomics data, we identified cell–cell adhesion as the molecular event upstream the pathway involved in the anchoring and retention at the PM. We show that by interacting with NIS at the PM, adherens junction (AJ)-associated P120-catenin recruits and is phosphorylated by SRC, allowing it to recruit RAC1 to the complex. This enables SRC-phosphorylated VAV2 exchange factor to activate RAC1 GTPase, inducing NIS retention at the PM, thus increasing its abundance and function at the surface of thyroid cells. Our findings indicate that the loss of epithelial cell–cell adhesion may contribute to RAI refractoriness, indicating that in addition to stimulating NIS expression, successful resensitization therapies might require the employment of agents that improve cell–cell adhesion and NIS PM retention in refractory TC cells. | pt_PT |
| dc.description.sponsorship | This work was funded by Bolsa Edward Limbert Merck/SPEDM-2021 (grant Limbert2021 from Merck/SPEDM, Portugal) and Fundação para a Ciência e a Tecnologia (FCT), Portugal, through grants PTDC/BIAMOL/31787/2017 (to ALS and PM) and UID/MULTI/04046/2019 (to BioISI). MF was the recip | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Cancers (Basel). 2022 Oct 31;14(21):5362. doi: 10.3390/cancers14215362 | pt_PT |
| dc.identifier.doi | 10.3390/cancers14215362 | pt_PT |
| dc.identifier.issn | 2072-6694 | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/8413 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | MDPI | pt_PT |
| dc.relation | Sodium-iodide symporter posttranslational interactome: identification of novel targets to enhance iodide-related cancer therapy | |
| dc.relation | Biosystems & Integrative Sciences Institute | |
| dc.relation.publisherversion | https://www.mdpi.com/2072-6694/14/21/5362 | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt_PT |
| dc.subject | Thyroid Carcinoma | pt_PT |
| dc.subject | Thyroid Cancer | pt_PT |
| dc.subject | RAI-refractory | pt_PT |
| dc.subject | NIS | pt_PT |
| dc.subject | Adherens Junctions | pt_PT |
| dc.subject | Plasma Membrane Localization | pt_PT |
| dc.subject | Vias de Transdução de Sinal e Patologias Associadas | pt_PT |
| dc.title | Adherens Junction Integrity Is a Critical Determinant of Sodium Iodide Symporter Residency at the Plasma Membrane of Thyroid Cells | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.awardTitle | Sodium-iodide symporter posttranslational interactome: identification of novel targets to enhance iodide-related cancer therapy | |
| oaire.awardTitle | Biosystems & Integrative Sciences Institute | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-MOL%2F31787%2F2017/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04046%2F2019/PT | |
| oaire.citation.issue | 21 | pt_PT |
| oaire.citation.startPage | 5362 | pt_PT |
| oaire.citation.title | Cancers | pt_PT |
| oaire.citation.volume | 14 | pt_PT |
| oaire.fundingStream | 3599-PPCDT | |
| oaire.fundingStream | 6817 - DCRRNI ID | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.embargofct | Acesso de acordo com política editorial da revista. | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |
| relation.isProjectOfPublication | 21f29b04-5f25-4fca-89e1-3ebf685647df | |
| relation.isProjectOfPublication | 35168786-8dfc-4a00-9759-dab3669fe1ae | |
| relation.isProjectOfPublication.latestForDiscovery | 21f29b04-5f25-4fca-89e1-3ebf685647df |