The Smad family and its role in pancreatic cancer

One of the major signaling pathways that determine the tumor aggression and patient outcome in pancreatic cancer is the transforming growth factor-beta (TGF-beta) pathway. It is inactivated at various levels in pancreatic cancer and plays a dual role in tumor initiation and progression. The Smad family of proteins transduce signals from the TGF-beta superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. This review discusses the structure, function and regulation of various participating Smad family members, and their individual roles in determining the progression and outcome of pancreatic cancer patients, with a special emphasis on Smad4.