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

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.

Pancreatic cancer tumor microenvironment is a major therapeutic barrier and target

“…Down-regulation of the cell-to-cell adhesion marker, e-cadherin, along with upregulation of n-cadherin and vimentin denote EMT progression ( 33 ). Key transcription factors traditionally upregulated in PDAC mesenchymal cells includes SNAIL, SLUG, TWIST1, Zeb1, and 2 ( 34 ). Many of such transcription factors being linked to increased mobility and commonly observed in circulating tumor cells.…”

Role of exosomes in non-small cell lung cancer and EGFR-mutated lung cancer

“…Tumor metastasis is a complex process that involves the transformation of quiescent epithelial cells into motile cells and the invasion of other organs, a phenomenon known as EMT. EMT is a process in which polarized epithelial cells (mostly interacting with the basement membrane through their basal surface) undergo a variety of biochemical changes that result in a mesenchymal cell phenotype, including increased migratory and invasive capacity, increased resistance to apoptosis, and increased production of ECM components (105)(106)(107). EMT is signaled by the degradation of the underlying basement membrane and the formation of mesenchymal cells, allowing migration of mesenchymal cells from their origin to the upper cortex.…”

NIFK as a potential prognostic biomarker in colorectal cancer correlating with immune infiltrates

“…Metastasis and recurrence play a vital role in CRC progression and associated with immune parameters in patients. [ 10 ] As showed in many studies, [ 11 – 13 ] epithelial-mesenchymal transition played a critical role in the tumor metastasis and tumor microenvironment including immune landscape contributed epithelial-mesenchymal transition development. [ 14 ] Immune related IL-6/STAT3 pathway with its downstream genes could drive tumor invasion and metastasis along with drug resistance.…”