TGF-L1 and Smad4 overexpression induce a less invasive phenotype in highly invasive spindle carcinoma cells

Abstract

We have examined the effect of transforming growth factor L1 (TGF-L1) and overexpression of the Smad4 gene on the phenotype of Car C, a ras mutated highly malignant spindle carcinoma cell line. TGF-L1-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-L1 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-L1 and Smad4 overexpression reduce the invasive potential of Car C cells, probably via the Smad pathway. ' 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.