It has been suggested that such plastic states are related to cancer stem cell phenotypes.7,15,57 In addition, our finding on the causal influence of ZEB1 on key EMT genes, such as SNAIL and TWIST1/2, provides a possible explanation for the differential effects of knocking out ZEB1, SNAIL, and TWIST in mouse model of pancreatic cancer.16,53 ZEB1 was considered a gene downstream of SNAIL and TWIST,58,59 and our results show that ZEB1 can be a key regulator broadly influencing M-genes, including SNAIL and TWIST. Here, ZEB1 is linked to familial pancreatic carcinoma.