Lastly, SMAD4 as a transcription factor was the central mediator of TGF-β signaling, and it broadly interacted with many classical pathways, such as MAPK, PI3K/AKT and WNT/β-catenin, forming a complex network responsible for a wide range of cellular processes, such as proliferation, differentiation, apoptosis and migration, as well as cancer initiation and development [52]. This evidence concerns the gene SMAD4 and cancer.