SMAD3 and neoplasm: However, neither SMAD2 nor SMAD3 were found to be phosphorylated on PANC-1 treated with GEM/NAB + CM-HMC-1.Recently, a functional cooperativity between TGF-β1 and PAR2 has been demonstrated on several cellular responses to tumor microenvironment in PDAC, such as induction of fibrosis, cell motility and invasion [27,28].