Nuclear translocation of β-catenin represses membrane localization of NIS in human thyroid cancer cells

Abstract

To explore whether nuclear translocation of β-catenin affects functional expression of sodium iodide symporter (NIS) in human thyroid cancer cells. Two kinds of β-catenin nuclear translocation cell models were firstly established with transfection of hypoxia inducible factor 1α (HIF-1α) and β-catenin cDNA in human thyroid cancer cell line FTC133. Then the expression of β-catenin were further interfered by shRNA in above two cell models. After that, the influence of β-catenin nuclear localization on the functional expression of NIS, iodine uptake potency, epithelial-mesenchymal transition (EMT) characteristics, tumor growth curve and treatment effect inducing by radioactive iodine were comparatively analyzed in vitro and in vivo trials. Additionally, the underlying mechanism of NIS functional expression was also assessed via identifying the activation of β-catenin signal pathway. In vitro assay showed prominent EMT phenotype in the above two β-catenin nuclear translocation cell models, and in vitro proliferation and invasion potential of cancer cells markedly increased (all P<0.05); NIS protein expression translocated from cell membrane to cytoplasma. Cell iodide uptake in vitro decreased about 50.0% and 37.5%, respectively in above two β-catenin translocation cell models (both P<0.05). Moreover, β-catenin nuclear translocation was correlated with phosphorylation expressions of β-catenin Ser45, Y654 and GSK-3β Ser9. Most importantly, all above changes associated with β-catenin nuclear translocation could be effectively reversed after blockade of β-catenin expression. In the animal model, tumor growth potential and tumor mass were significantly inhibited by both blockade of β-catenin and radioactive iodide ((131)I) (all P<0.05). Meanwhile, immunohistochemistry demonstrated that β-catenin nuclear translocation remained in subcutaneous tumor cells after transplantation, and showed negatively associated with NIS membrane expression. β-catenin nuclear translocation is a vital regulatory pathway involved in functional expression of NIS in human thyroid cancer cells.