SMAD6 and neoplasm: Several negative regulators of the TGF-β pathway, for example, prostate transmembrane protein androgen-induced 1 (PMEPA1) [40] and thrombospondin-1 (THBS1) [41, 42], certain I-Smads (i.e., Smad6 and Smad7), Smad ubiquitination regulatory factors (Smurfs) [43], and TG-interacting factor (TGIF) [44], have been shown to be tumor suppressors.