Smad7 inhibits the survival nuclear factor kappa B and potentiates apoptosis in epithelial cells

In this study, we examined the effect of the stable expression of Smad7 in two different cell lines on apoptosis induced by various stimuli including TGF-beta, serum withdrawal, loss of cell adhesion (anoikis) and TNF-alpha. Smad7 increased TGF-beta -mediated apoptosis in Mv1Lu cells as well as anoi kis and/or serum withdrawal-induced apoptosis in Mv1Lu and MDCK cells. Smad 7 markedly decreased the activity of the survival NF-kappaB transcription f actor in MDCK cells, Interestingly, the stable expression of oncogenic Ras in MDCK cells which suppressed Smad7 inhibition of NF-kappaB also suppresse d Smad7 potentiation of serum withdrawal-induced apoptosis and anoikis, In addition, Smad7 inhibited TNF-alpha stimulation of NF-kappaB and increased TNF-alpha -mediated apoptosis in MDCK cells. Our results provide the first evidence that Smad7 induces sensitization of cells to different forms of ce ll death. They moreover demonstrate that Smad7 inhibits the survival NF-kap paB factor, providing a potential mechanism whereby Smad7 potentiates cell death.