SKIP is required for TGF-β1-induced epithelial mesenchymal transition and migration in transformed keratinocytes.
Transforming growth factor-β1 (TGF-β1) potently induces the epithelial-mesenchymal transition (EMT) during tumoral progression. Although Sky-interacting protein (SKIP) regulates TGF-β1-induced Smad activation, its role in the induction of cell malignance remains uncertain. We found that TGF-β1 increases SKIP expression in PDV cells. In cells stably transfected with SKIP antisense, AS-S, Smad3 activation decreased, along with an inhibition of TGF-β1-induced EMT, and the cells were sensitized to the TGF-β1-dependent inhibition of proliferation. Also, AS-S cells showed a weaker migration and invasion response. Moreover, TGF-β1-induced urokinase-type plasminogen activator expression was inhibited, concomitantly with a TGF-β1-independent increment of the plasminogen-activator inhibitor-1 expression. Thus, these results suggest that SKIP is required for EMT and invasiveness induced by TGF-β1 in transformed cells.
Villar
Victor
V
Laboratorio de Biología Celular, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile.
Kocic
Jelena
J
Bugarski
Diana
D
Jovcic
Gordana
G
Santibanez
Juan F
JF
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics
D009687:Nuclear Proteins; D017395:Plasminogen Activator Inhibitor 1; C491762:Skiip protein, mouse; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D014568:Urokinase-Type Plasminogen Activator