TGF-β1 and Smad4 overexpression induce a less invasive phenotype in highly invasive spindle carcinoma cells

Abstract

We have examined the effect of transforming growth factor β1 (TGF-β1) and overexpression of the Smad4 gene on the phenotype of Car C, a ras mutated highly malignant spindle carcinoma cell line. TGF-β1-treated Car C cells overexpressing Smad4 spread with a flattened morphology with membrane ruffles abundant in vinculin and show a reduction in their invasive abilities. TGF-β1 treatment and overexpression of Smad4 also enhanced the production of PAI-1 measured by the activation of the p3TP-lux reporter gene containing a PAI-1-related promoter. This activation was abolished with a dominant-negative Smad4 construct. These results lead us to conclude that both TGF-β1 and Smad4 overexpression reduce the invasive potential of Car C cells, probably via the Smad pathway.