SMAD4 and neoplasm: Because the tumor suppressive activity of TGF-β signaling is believed to be mediated by the Smad-dependent pathway and Smad4 plays a central role in TGF-β-induced Smad transcriptional activity, we knocked down Smad4 in HCC cells to elucidate the pathway(s) that mediates autocrine TGF-β/TβRII-induced cell survival.