SMAD4 and pancreatic ductal adenocarcinoma: Transforming growth factor β signaling also plays a vital role in cell growth, differentiation, apoptosis, migration, initiation, and progression of cancer.[18] Studies have reported that SMAD4, a central mediator of transforming growth factor-β signaling, is mutated or deleted in 20% of pancreatic ductal adenocarcinomas, significantly affecting cancer development.