Thyroid hormone promotes cell invasion through activation of furin expression in human hepatoma cell lines

The objective of this study was to identify genes regulated by thyroid hormone (T-3) and associated with tumor invasion. The gene encoding furin, as previously identified by cDNA microarray, is known to be up-regulated by T-3 treatment, and stimulated furin production occurs in thyroidectomized rats after administration of T-3. Presently, by using serial deletion of the promoter and EMSAs, the T-3 response element on the furin promoter was localized to the -6317/-6302 region. T-3-mediated furin up-regulation was cooperative with TGF-beta because T-3 induction increased after Smad3/4 addition. Furthermore, the invasiveness of HepG2-thyroid hormone receptor (TR) cells was significantly increased by T-3 treatment, perhaps due to furin processing of matrix metalloproteinase-2 and -9. In addition, furin up-regulation either by stable overexpression