Targeting TGF-β1 inhibits invasion of anaplastic thyroid carcinoma cell through SMAD2-dependent S100A4-MMP-2/9 signalling.

OBJECTIVE Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies. However, the molecular mechanisms of ATC invasion are poorly understood. The transforming growth factor-beta (TGF-β) signaling pathway plays a critical role in promoting tumor metastasis. TGF-β1 was found to be overexpressed in anaplastic thyroid cancer (ATC). We therefore tested our hypothesis that targeted down-regulation of TGF-β1 inhibits invasion of ATC cells. METHODS Effects of TGF-β1 stimulation or TGF-β1 sliencing by small interfering RNA (TGF-β1 siRNA) on invasion in 8505C and SW1736 cells in vitro was detected. Using siRNAs and inhibitors to examine the TGF-β1 signaling pathway. RESULTS TGF-β1 siRNA inhibits cell migration and invasion in vitro, followed by inactivation of pSMAD2, S100A4 and MMP-2/9. TGF-β stimulation activated pSMAD2-dependent S100A4 and MMP-2/9 expression, and increased cell migration and invasion. The depletion of pSMAD2 or S100A4 or MMP-2/9 expression inhibited TGF-β signaling pathway. Moreover, it significantly weakened the proinvasive effects of TGF-β on ATC cells. CONCLUSIONS Therapies targeting the TGF-β1 inhibits invasion of ATC cells by impeding the SMAD2-dependent S100A4-MMP-2/9 signalling in vitro.