SMAD4 and neoplasm: The TGF-β signaling pathway plays a complex role in the development of CRC, acting as a double-edged sword that can both inhibit tumor formation and promote tumor progression.13,14 SMAD4 protein plays a pivotal role in this pathway, where its loss of function not only affects cell cycle regulation and apoptosis but can also lead to cellular evasion of growth inhibitory signals, thereby promoting tumor development.