Abstract
In this study, we aimed to investigate the biological functions of Tuftelin 1 (Tuft1) in thyroid carcinoma (TC) and determine its underlying molecular mechanism. We found that the expression of Tuft1 was significantly upregulated in TC tissues. Using TC tissue microarrays (n = 154), we found that Tuft1 expression was closely related with the overall survival (OS) and disease-free survival (DFS) of TC patients. Knockdown of Tuft1 in TPC-1 and SW579 cells suppressed the invasion and proliferation of TC cells and increased the apoptosis of TC cells. In vivo, knockdown of Tuft1 attenuated tumor growth and suppressed the phosphorylation of Akt, mTOR, and GSK3β signaling. Addition of recombinant Tuft1 protein (rTuft1) to TC cells increased the phosphorylation of Akt, mTOR, and GSK3β signaling. An mTOR inhibitor (Dactolisib) abrogated rTuft1 protein-induced TC cell invasion, proliferation, and apoptosis inhibition, whereas a GSK3β inhibitor (CHIR-98014) only abrogated rTuft1 protein-induced proliferation and apoptosis inhibition. These results suggest that Tuft1 promotes TC cell invasion and proliferation, and suppresses apoptosis through the Akt-mTOR or Akt-GSK3β signaling pathway. In the future, Tuft1 may serve as a potential therapeutic target for TC.