Smad4 expression knockdown, performed by means of RNA interference, or transfection with a dominant negative mutant form of Smad4, resulted in preserved E-cadherin expression in a pancreatic cancer cell line [88], suppression of type I collagen synthesis in vitro, fibrotic process features, and decreased bone metastasis in vivo [89]. Here, SMAD4 is linked to familial pancreatic carcinoma.