Our work reveals that the GSI can selectively block epithelial-mesenchymal transition (EMT), migration and invasion in human pancreatic cancer cell lines, and can suppress pancreatic tumor initiating CD44+/EpCAM+ cells in a xenograft mouse model.These findings support the development of therapeutic strategies targeting Notch signalling in pancreatic cancer. This evidence concerns the gene CD44 and familial pancreatic carcinoma.