New Insights into the Crossroads between EMT and Stemness in the Context of Cancer.

Isabel Fabregat,Jitka Soukupova,Andrea Malfettone

doi:10.3390/jcm5030037

Abstract

The epithelial-mesenchymal transition (EMT) is an example of cellular plasticity, where an epithelial cell acquires a mesenchymal-like phenotype that increases its migratory and invasive properties. Stemness is the ability of stem cells to proliferate in an asymmetric way that allows them to maintain the reservoir of undifferentiated cells with stem cell identity, but also to produce new differentiated cells. Initial works revealed that activation of the EMT program in epithelial cells induces the acquisition of stem cell properties, which in the context of cancer may contribute to the appearance of tumor initiating cells (TIC). However, a number of groups have recently reported that mesenchymal-epithelial transition (MET) is required for efficient metastatic colonization and that EMT may be not necessarily associated with stemness. In this review, we summarize recent findings that extend our knowledge about the crossroads between EMT and stemness and their relevance under physiological or pathological conditions.

Highlights

Cellular plasticity refers to the ability of cells to reversibly change their phenotype [1]
Several phenomena associated with tumor progression are known to trigger expression of epithelial-mesenchymal transition (EMT)-Transcription Factors (TFs) [23]
The EMT phenotype is an example of cellular plasticity, where different intermediate situations may occur

Summary

Introduction

Cellular plasticity refers to the ability of cells to reversibly change their phenotype [1]. Several phenomena associated with tumor progression (inflammation, metabolic stress, or abnormal activation of signaling pathways, such as those controlled by TGF-β, Wnt, and Notch, among others) are known to trigger expression of EMT-TFs [23] These pathways are susceptible to gain-of-function mutations or constitutive signal activation that would force transition toward a mesenchymal phenotype [24]. Later proposed that activation of the EMT program in non-transformed epithelial cells confers properties of SC [5] In this sense, chronic treatment of human fetal hepatocytes with TGF-β induces a mesenchymal phenotype concomitant with loss in the expression of specific hepatic genes and appearance of SC markers, reminiscent of progenitor-like cells [34]. The way in which EMT and stemness are connected, as well as its relevance for the metastatic process, are still controversial issues in tumorigenesis

EMT and Stemness

Epithelial Plasticity

EMT and Stemness in the Crossroads of Chemotherapy Resistance

Concluding Remarks