Epithelial to Mesenchymal Transition: A Challenging Playground for Translational Research. Current Models and Focus on TWIST1 Relevance and Gastrointestinal Cancers

Abstract

Resembling the development of cancer by multistep carcinogenesis, the evolution towards metastasis involves several passages, from local invasion and intravasation, encompassing surviving anoikis into the circulation, landing at distant sites and therein establishing colonization, possibly followed by the outgrowth of macroscopic lesions. Within this cascade, epithelial to mesenchymal transition (EMT) works as a pleiotropic program enabling cancer cells to overcome local, systemic, and distant barriers against diffusion by replacing traits and functions of the epithelial signature with mesenchymal-like ones. Along the transition, a full-blown mesenchymal phenotype may not be accomplished. Rather, the plasticity of the program and its dependency on heterotopic signals implies a pendulum with oscillations towards its reversal, that is mesenchymal to epithelial transition. Cells in intermixed EÛM states can also display stemness, enabling their replication together with the epithelial reversion next to successful distant colonization. If we aim to include the EMT among the hallmarks of cancer that could modify clinical practice, the gap between the results pursued in basic research by animal models and those achieved in translational research by surrogate biomarkers needs to be filled. We review the knowledge on EMT, derived from models and mechanistic studies as well as from translational studies, with an emphasis on gastrointestinal cancers (GI).

TWIST1 is a prognostic factor for neoadjuvant chemotherapy for patients with resectable pancreatic cancer: a preliminary study

“…Future studies should explore molecular reasons for these results in greater detail. Second, TWIST1 mainly played a role in stemness and chemoresistance rather than progression and metastasis, although SNAIL and ZEB1 played roles in invasion and metastasis [ 29 ]. TWIST1 overexpression also led to an undifferentiated status and the activation of the ras-signaling pathway [ 29 ].…”

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

“…Considering the modifications of the cells composing the complex array of tumor microenvironment, it should not be disregarded that epithelial cells acquiring plasticity can also assume the features of other cells. Such changes along EMT implicate cellular de-differentiation and an increase in motility following the loss of cell–cell adhesion [ 15 ]. Ideally, in the reverse change referred to as mesenchymal–epithelial transition (MET), cells lose migratory freedom, re-expressing junction complexes and again adopting apicobasal polarity [ 16 ].…”

“…Several master transcription factors (TFs) can activate the EMT [ 7 , 15 ]. Among these, TWIST1 plays an essential role both in normal development and cancer metastasis [ 61 ].…”

The emerging roles of exosomal long non‐coding RNAs in bladder cancer

“…These transcription factors can inhibit the expression of epithelial marker E-cadherin and increase the mesenchymal marker N-cadherin expression to promote EMT. 90 Besides, EMT can also be regulated by several diverse upstream regulators, including signalling molecules and exosomal lncRNAs by various mechanisms.…”