{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:25:37Z","timestamp":1792808737772,"version":"4.5.0"},"reference-count":119,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"publisher","award":["JP23K06456"],"award-info":[{"award-number":["JP23K06456"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"award":["JP23K06456"],"award-info":[{"award-number":["JP23K06456"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Signal transducers and activators of transcription (STAT) proteins, which operate via canonical and non-canonical mechanisms, are critically implicated in thyroid tumorigenesis. This review integrates their multifaceted roles in thyroid cancer. STAT3 acts as a \u201cdouble-edged sword\u201d: hyperactive STAT3 drives metastasis and BRAF inhibitor resistance in advanced carcinomas, yet paradoxically acts as a tumor suppressor by restraining the Warburg effect via non-canonical mitochondrial localization. Clinically, preserved nuclear STAT3 independently predicts a favorable prognosis and is inversely correlated with TERT promoter mutations, offering a biological modifier for clinical risk stratification. Furthermore, STAT1 regulates differentiation via the IGF2BP2-m6A axis, STAT5 drives proliferation upon release from TR\u03b2 suppression, and STAT6 confers chemoresistance. While novel direct STAT3 inhibitors (e.g., TTI-101) and rational combinations with immune checkpoint inhibitors or STING agonists show promise in overcoming refractory disease, the intricate dual functionality of STAT family proteins demands rigorous biomarker-guided precision medicine approaches.<\/jats:p>","DOI":"10.3390\/cells15100884","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T06:42:18Z","timestamp":1779691338000},"page":"884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Roles of STAT3 and STAT Family Proteins and Their Signaling Pathways in Thyroid Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5959-6182","authenticated-orcid":false,"given":"Chie","family":"Masaki","sequence":"first","affiliation":[{"name":"Department of Pathology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan"},{"name":"Department of Surgery, Ito Hospital, Tokyo 150-8308, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0017-5086","authenticated-orcid":false,"given":"Norihito","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4374-9997","authenticated-orcid":false,"given":"Tomohiro","family":"Chiba","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan"},{"name":"Department of Cytology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1158\/1055-9965.EPI-21-1440","article-title":"Cancer Progress and Priorities: Epidemiology of Thyroid Cancer","volume":"31","author":"Kitahara","year":"2022","journal-title":"Cancer Epidemiol. 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