An intriguing work by Gatza and colleagues reported that overexpression of TβRIII betaglycan in colon cancer cells enhances both canonical and non-canonical TGF-β signaling by inducing TGF-β-dependent phosphorylation of SMAD2 and p38 while inhibiting TGF-β -induced p21 and p27 expression. This evidence concerns the gene TGFB1 and colonic neoplasm.