Knockdown experiments suggested that SMAD4 was not necessary (Levy et al., 2007), but we subsequently showed that tumor cells deleted for SMAD4 or containing mutations in SMAD4 that abolish interactions with activated R-SMADs, abrogated TGF-β-induced degradation of SKI/SKIL (Briones-Orta et al., 2013). Here, TGFB1 is linked to neoplasm.