{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:18Z","timestamp":1784557218237,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>Thyroid cancer (TC) is the most common endocrine malignancy. The sodium\u2013iodide 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.<\/jats:p>","DOI":"10.1530\/jme-19-0195","type":"journal-article","created":{"date-parts":[[2019,10,7]],"date-time":"2019-10-07T12:23:40Z","timestamp":1570451020000},"page":"309-320","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":12,"title":["Antagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroid"],"prefix":"10.1530","volume":"63","author":[{"given":"M\u00e1rcia","family":"Faria","sequence":"first","affiliation":[{"name":"1Servi\u00e7o de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universit\u00e1rio de Lisboa Norte-Hospital Santa Maria, Lisboa, Portugal"},{"name":"2BioISI \u2013 Biosystems and Integrative Sciences Institute, Faculdade de Ci\u00eancias da Universidade de Lisboa, Lisboa, Portugal"},{"name":"3Departamento de Gen\u00e9tica Humana, Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge, Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"F\u00e9lix","sequence":"additional","affiliation":[{"name":"1Servi\u00e7o de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universit\u00e1rio de Lisboa Norte-Hospital Santa Maria, Lisboa, Portugal"},{"name":"4ISAMB \u2013 Instituto de Sa\u00fade Ambiental, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Domingues","sequence":"additional","affiliation":[{"name":"1Servi\u00e7o de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universit\u00e1rio de Lisboa Norte-Hospital Santa Maria, Lisboa, Portugal"},{"name":"4ISAMB \u2013 Instituto de Sa\u00fade Ambiental, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jo\u00e3o","family":"Bugalho","sequence":"additional","affiliation":[{"name":"1Servi\u00e7o de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universit\u00e1rio de Lisboa Norte-Hospital Santa Maria, Lisboa, Portugal"},{"name":"5Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo","family":"Matos","sequence":"additional","affiliation":[{"name":"2BioISI \u2013 Biosystems and Integrative Sciences Institute, Faculdade de Ci\u00eancias da Universidade de Lisboa, Lisboa, Portugal"},{"name":"3Departamento de Gen\u00e9tica Humana, Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge, Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Lu\u00edsa","family":"Silva","sequence":"additional","affiliation":[{"name":"1Servi\u00e7o de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universit\u00e1rio de Lisboa Norte-Hospital Santa Maria, Lisboa, Portugal"},{"name":"4ISAMB \u2013 Instituto de Sa\u00fade Ambiental, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Molecular Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/jme.bioscientifica.com\/view\/journals\/jme\/63\/4\/JME-19-0195.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jme.bioscientifica.com\/downloadpdf\/journals\/jme\/63\/4\/JME-19-0195.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:53:49Z","timestamp":1784555629000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/jme\/article\/63\/4\/309-320\/14371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11]]},"references-count":0,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1530\/jme-19-0195","relation":{},"ISSN":["0952-5041","1479-6813"],"issn-type":[{"value":"0952-5041","type":"print"},{"value":"1479-6813","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11]]}}}