Chapter 7
Mesenchymal-to-Epithelial Transitions in Development
and Cancer
John-Poul Ng-Blichfeldt and Katja Ro ¨ per
Abstract
The evolutionary emergence of the mesenchymal phenotype greatly increased the complexity of tissue
architecture and composition in early Metazoan species. At the molecular level, an epithelial-to-mesenchymal transition (EMT) was permitted by the innovation of specific transcription factors whose expression is
sufficient to repress the epithelial transcriptional program. The reverse process, mesenchymal-to-epithelial
transition (MET), involves direct inhibition of EMT transcription factors by numerous mechanisms
including tissue-specific MET-inducing transcription factors (MET-TFs), micro-RNAs, and changes to
cell and tissue architecture, thus providing an elegant solution to the need for tight temporal and spatial
control over EMT and MET events during development and adult tissue homeostasis.
Key words Epithelial morphogenesis, MET, Apical-basal polarity, Transcription factors
1 Introduction
Epithelial and mesenchymal cells represent the two major cell types
within triploblastic Metazoan organisms. Epithelial cells are defined
as cells forming continuous sheets with apical-basal polarity, and
that possess a low degree of individual motility due to strong
intercellular adhesive forces via apical-lateral tight junctions (TJs),
adherens junctions (AJs), and desmosomal complexes, and basal
interactions with extracellular matrix (ECM) via cell-matrix junctions [1]. Conversely, mesenchymal cells are capable of a high
degree of motility due to an absence of stable intercellular and
cell-matrix adhesive complexes, and possess front-back instead of
apical-basal polarity. It is now recognized, however, that these
definitions reflect extreme ends of a spectrum of phenotypes that
includes a variety of cell states with intermediate levels of junctional
complexity, and varying capabilities for either individual or collective motility [2]. Consequently, plasticity between the epithelial
and mesenchymal state is an intensive area of research; both
Kyra Campbell and Eric Theveneau (eds.), The Epithelial-to Mesenchymal Transition: Methods and Protocols,
Methods in Molecular Biology, vol. 2179, https://doi.org/10.1007/978-1-0716-0779-4_7,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
43
Mesenchymal-to-Epithelial Transitions in Development
and Cancer
John-Poul Ng-Blichfeldt and Katja Ro ¨ per
Abstract
The evolutionary emergence of the mesenchymal phenotype greatly increased the complexity of tissue
architecture and composition in early Metazoan species. At the molecular level, an epithelial-to-mesenchymal transition (EMT) was permitted by the innovation of specific transcription factors whose expression is
sufficient to repress the epithelial transcriptional program. The reverse process, mesenchymal-to-epithelial
transition (MET), involves direct inhibition of EMT transcription factors by numerous mechanisms
including tissue-specific MET-inducing transcription factors (MET-TFs), micro-RNAs, and changes to
cell and tissue architecture, thus providing an elegant solution to the need for tight temporal and spatial
control over EMT and MET events during development and adult tissue homeostasis.
Key words Epithelial morphogenesis, MET, Apical-basal polarity, Transcription factors
1 Introduction
Epithelial and mesenchymal cells represent the two major cell types
within triploblastic Metazoan organisms. Epithelial cells are defined
as cells forming continuous sheets with apical-basal polarity, and
that possess a low degree of individual motility due to strong
intercellular adhesive forces via apical-lateral tight junctions (TJs),
adherens junctions (AJs), and desmosomal complexes, and basal
interactions with extracellular matrix (ECM) via cell-matrix junctions [1]. Conversely, mesenchymal cells are capable of a high
degree of motility due to an absence of stable intercellular and
cell-matrix adhesive complexes, and possess front-back instead of
apical-basal polarity. It is now recognized, however, that these
definitions reflect extreme ends of a spectrum of phenotypes that
includes a variety of cell states with intermediate levels of junctional
complexity, and varying capabilities for either individual or collective motility [2]. Consequently, plasticity between the epithelial
and mesenchymal state is an intensive area of research; both
Kyra Campbell and Eric Theveneau (eds.), The Epithelial-to Mesenchymal Transition: Methods and Protocols,
Methods in Molecular Biology, vol. 2179, https://doi.org/10.1007/978-1-0716-0779-4_7,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
43