“In medio stat virtus”: Insights into hybrid E/M phenotype attitudes

Abstract

Epithelial-mesenchymal plasticity (EMP) refers to the ability of cells to dynamically interconvert between epithelial (E) and mesenchymal (M) phenotypes, thus generating an array of hybrid E/M intermediates with mixed E and M features. Recent findings have demonstrated how these hybrid E/M rather than fully M cells play key roles in most of physiological and pathological processes involving EMT. To this regard, the onset of hybrid E/M state coincides with the highest stemness gene expression and is involved in differentiation of either normal and cancer stem cells. Moreover, hybrid E/M cells are responsible for wound healing and create a favorable immunosuppressive environment for tissue regeneration. Nevertheless, hybrid state is responsible of metastatic process and of the increasing of survival, apoptosis and therapy resistance in cancer cells. The present review aims to describe the main features and the emerging concepts regulating EMP and the formation of E/M hybrid intermediates by describing differences and similarities between cancer and normal hybrid stem cells. In particular, the comprehension of hybrid E/M cells biology will surely advance our understanding of their features and how they could be exploited to improve tissue regeneration and repair.

Epithelial–mesenchymal plasticity in kidney fibrosis

“…Many mammalian cells can change their phenotype by a process called cellular plasticity (Bar‐Hai & Ishay‐Ronen, 2022; Canciello et al, 2022; Horsley, 2022; Merrell & Stanger, 2016). These cells are capable of differentiation toward mature stage and, on the other hand, can dedifferentiate or transdifferentiate to exhibit new phenotypes (Bar‐Hai & Ishay‐Ronen, 2022; Canciello et al, 2022; Horsley, 2022; Merrell & Stanger, 2016). Epithelial cells also undergo epithelial–mesenchymal plasticity (EMP) with dynamic changes in cellular structure, composition, and function, becoming mixed (hybrid) epithelial/mesenchymal (E/M) phenotypes (Canciello et al, 2022; Yang et al, 2020).…”

“…These cells are capable of differentiation toward mature stage and, on the other hand, can dedifferentiate or transdifferentiate to exhibit new phenotypes (Bar‐Hai & Ishay‐Ronen, 2022; Canciello et al, 2022; Horsley, 2022; Merrell & Stanger, 2016). Epithelial cells also undergo epithelial–mesenchymal plasticity (EMP) with dynamic changes in cellular structure, composition, and function, becoming mixed (hybrid) epithelial/mesenchymal (E/M) phenotypes (Canciello et al, 2022; Yang et al, 2020). Under both physiologic and pathologic conditions, the cells can stay in this intermediate state within the hybrid E/M spectrum.…”

“…EMP involves epithelial–mesenchymal transition (EMT) and the reverse process, mesenchymal–epithelial transition (MET). EMP is thus an important process to allow the cells to progress toward epithelial–mesenchymal axis and to maintain their intermediate hybrid E/M state (Canciello et al, 2022; Yang, Antin, et al, 2020). In addition to EMT and MET, endothelial‐mesenchymal transition (EndoMT or EndMT) is another cellular plasticity process widely studied (Canciello et al, 2022; Yang, Antin, et al, 2020).…”

“…EMP is thus an important process to allow the cells to progress toward epithelial–mesenchymal axis and to maintain their intermediate hybrid E/M state (Canciello et al, 2022; Yang, Antin, et al, 2020). In addition to EMT and MET, endothelial‐mesenchymal transition (EndoMT or EndMT) is another cellular plasticity process widely studied (Canciello et al, 2022; Yang, Antin, et al, 2020). In this review, we focus on the EMT process in tubular epithelial cells (TECs) and podocytes and its roles in renal tubulointerstitial fibrosis (TIF) and glomerulosclerosis, respectively, both of which lead to kidney fibrosis and chronic kidney disease (CKD; Figure 1).…”

“…Many mammalian cells can change their phenotype by a process called cellular plasticity (Bar‐Hai & Ishay‐Ronen, 2022; Canciello et al, 2022; Horsley, 2022; Merrell & Stanger, 2016). These cells are capable of differentiation toward mature stage and, on the other hand, can dedifferentiate or transdifferentiate to exhibit new phenotypes (Bar‐Hai & Ishay‐Ronen, 2022; Canciello et al, 2022; Horsley, 2022; Merrell & Stanger, 2016).…”