{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:58:33Z","timestamp":1753869513321,"version":"3.41.2"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Metastasis is the trigger of death in anaplastic thyroid cancer (ATC) patients, yet the specific mechanisms at play are still largely enigmatic. While the involvement of <jats:italic>LARP1<\/jats:italic> in the metastatic process of various cancers has been documented, there is a noticeable gap in the literature regarding its potential influence on ATC metastasis. Molecular studies probed <jats:italic>LARP1<\/jats:italic> expression within ATC cells, with subsequent <jats:italic>in vitro<\/jats:italic> experiments examining the effects of <jats:italic>LARP1<\/jats:italic> on ATC cell metastasis and the mTOR signaling cascade. A suite of assays, including colony formation, scratch wound healing, transwell invasion, and cell adhesion, was used to assess cell growth, movement, invasion, and attachment. Western Blot determined the expression levels of epithelial\u2013mesenchymal transition (EMT) markers (E\u2010cadherin, Vimentin, N\u2010cadherin) and proteins implicated in metastasis (MMP\u20102, MMP\u20109), along with mTOR and p\u2010mTOR. The affinity of Telocinobufagin (TBG) from Yuanhua Toad Essence for <jats:italic>LARP1<\/jats:italic> was investigated through molecular docking, with CETSA assays providing subsequent validation. Further cellular experiments substantiated the influence of TBG on ATC cell metastasis and modulation in the mTOR pathway. <jats:italic>LARP1<\/jats:italic> levels were heightened in ATC cells, and its depletion effectively curbs their proliferative, migratory, invasive, and adhesive activities. With <jats:italic>LARP1<\/jats:italic> knockdown, we also observed that the onset of EMT and metastatic processes was thwarted, as was the mTOR pathway. Subsequent research has uncovered that TBG formed a physical complex with <jats:italic>LARP1<\/jats:italic>, allowing it to target and suppress the mTOR pathway, thus preventing the metastasis of ATC. The simultaneous overexpression of <jats:italic>LARP1<\/jats:italic>, however, lessened the ability of TBG to inhibit ATC metastasis. This study highlights the importance of TBG binding to <jats:italic>LARP1<\/jats:italic> in the mediation of the mTOR signaling pathway, a key process in the inhibition of ATC cell metastasis. This discovery introduces a new target for the diagnosis of ATC and enlightens the consideration of TBG as a treatment for ATC metastasis.<\/jats:p>","DOI":"10.1002\/kjm2.12934","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T13:40:18Z","timestamp":1736430018000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Telocinobufagin suppresses malignant metastasis of undifferentiated thyroid carcinoma via modulation of the <scp><i>LARP1<\/i><\/scp>\u2010<scp>mTOR<\/scp> pathway"],"prefix":"10.1002","volume":"41","author":[{"given":"Li\u2010Zhi","family":"Qiang","sequence":"first","affiliation":[{"name":"Department of Neck Surgery Sanming First Hospital Affiliated to Fujian Medical University  Sanming 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