SMAD4 and neoplasm: However, in PDAC alterations of TGFβ signaling through the mutation of genes involved in the pathway (e.g., SMAD4, SMAD3, TβR-I, TβR-II, ACVR1B, and ACVR2A), this role is present in 47% of cases [13], highlighting that TGFβ can sometimes acts as a tumor promoter.