Epithelial to Mesenchymal Transition as Mechanism of Progression of Pancreatic Cancer: From Mice to Men

SIMPLE SUMMARY: The progression of pancreatic cancer (PDAC) involves a series of events transforming the phenotype of cancer cells, namely epithelial-to-mesenchymal transition (EMT), which contributes to their invasiveness and spread. Although basic science studies, by in vitro and in vivo animal models strongly support the occurrence of EMT in PDAC, it remains perceived as something heretical in a clinical perspective. To turn this suspended perception, more translational data are needed, consolidating the notion of EMT as a hallmark of human PDAC. Clearly, the network of mechanisms involved its timing and regulation also requires further research, such as those aspects of EMT cancer cell at the intersection with stemness. The translational improvement provided by the identification of EMT markers suitable for deciphering the aggressive behavior of PDAC could eventually modify the clinical scenario, possibly contributing to the advancement in diagnosis and monitoring of its evolution and responsiveness to treatments. ABSTRACT: Owed to its aggressive yet subtle nature, pancreatic cancer remains unnoticed till an advanced stage so that in most cases the diagnosis is made when the cancer has already spread to other organs with deadly efficiency. The progression from primary tumor to metastasis involves an intricate cascade of events comprising the pleiotropic process of epithelial to mesenchymal transition (EMT) facilitating cancer spread. The elucidation of this pivotal phenotypic change in cancer cell morphology, initially heretic, moved from basic studies dissecting the progression of pancreatic cancer in animal models to move towards human disease, although no clinical translation of the concept emerged yet. Despite this transition, a full-blown mesenchymal phenotype may not be accomplished; rather, the plasticity of the program and its dependency on heterotopic signals implies a series of fluctuating modifications of cancer cells encompassing mesenchymal and epithelial features. Despite the evidence supporting the activation of EMT and MET during cancer progression, our understanding of the relationship between tumor microenvironment and EMT is not yet mature for a clinical application. In this review, we attempt to resume the knowledge on EMT and pancreatic cancer, aiming to include the EMT among the hallmarks of cancer that could potentially modify our clinical thinking with the purpose of filling the gap between the results pursued in basic research by animal models and those achieved in translational research by surrogate biomarkers, as well as their application for prognostic and predictive purposes.