In brief, KPC (SMAD4(+/+)) and KPDDC (SMAD4(−/−)) tumors showed increased RUNX3 expression levels and a high metastatic disease burden, and the high expression of RUNX3 was associated with increased metastatic potential of PDACs independent of epithelial-mesenchymal transition [8, 30]. Here, SMAD4 is linked to metastatic neoplasm.