Increasing evidence shows that the transferring of downstream TGF-β signaling from the canonical SMAD2/3:4 signaling cascade to non-canonical cascades (such as the mitogen-activated protein kinases (MAPKs), PI3K/AKT, rhodopsin (Rho) and TNF receptor-associated factor (TRAF) 4/6) may be a critical trigger for tumor promotion [38,39]. Here, SMAD2 is linked to neoplasm.