SMAD4 and cancer: In this study, we used SMAD4-proficient and -deficient human PDAC cell lines AsPC-1, CFPAC-1, and PANC-1 to compare the molecular profiles of SMAD4-positive and -negative PDAC cells; assess their relationship to SMAD4 status; and further demonstrate the ability of SMAD4 to modulate cell proliferation, affect cell motility, regulate the epithelial-mesenchymal-transition (EMT) process, activate kinase pathways, change expression of cancer stem-like cell (CSC) markers and affect sensitivity to chemodrugs in PDAC.