SKIP is required for TGF-beta 1-induced epithelial mesenchymal transition and migration in transformed keratinocytes

Abstract

Transforming growth factor-beta 1 (TGF-beta 1) potently induces the epithelial-mesenchymal transition (EMT) during tumoral progression. Although Sky-interacting protein (SKIP) regulates TGF-beta 1-induced Smad activation, its role in the induction of cell malignance remains uncertain. We found that TGF-beta 1 increases SKIP expression in PDV cells. In cells stably transfected with SKIP antisense, AS-S, Smad3 activation decreased, along with an inhibition of TGF-beta 1-induced EMT, and the cells were sensitized to the TGF-beta 1-dependent inhibition of proliferation. Also, AS-S cells showed a weaker migration and invasion response. Moreover, TGF-beta 1-induced urokinase-type plasminogen activator expression was inhibited, concomitantly with a TGF-beta 1-independent increment of the plasminogen-activator inhibitor-1 expression. Thus, these results suggest that SKIP is required for EMT and invasiveness induced by TGF-beta 1 in transformed cells.