epithelial-to-mesenchymal transitions (EMT) and mesenchymalto-epithelial transitions (MET) are integral to a wide range of
developmental and pathological processes. Here, we briefly discuss
the molecular and transcriptional control of MET events that occur
during development, and their implications for cancer metastasis.
2 Making and Breaking Epithelial Junctions
MET involves the stepwise formation of epithelial intercellular
contacts and establishment of apical-basal polarity (Fig. 1). While
the precise order of events is likely to be highly dependent on the
cell- and tissue-context, insight has predominantly come from cell
culture models in which epithelial cells establish apical-basal polarity (reviewed in [3, 4]). An early adhesion event between epithelial
(Àizing) cells is via the transmembrane protein nectin, which forms
calcium-independent hetero-trans-dimers between adjacent cells
[5]. Nectin complexes form scaffolds that recruit the actin-binding
protein afadin, and E-cadherin (CDH1), a prototypical member of
the cadherin family expressed by most epithelial cell types.
E-cadherin forms calcium-dependent homo-trans-dimers with
adjacent cells that progressively mature into AJs and are attached
to the intracellular actin cytoskeleton via alpha- and beta-catenin.
Basal
Apical
ECM
Immature AJ
Mature AJ
Cell-matrix junctions
Desmosome
TJ
Mesenchymal
Epithelial
A)
B)
C)
D)
Fig. 1 Potential mechanisms by which cells establish epithelial junctions during MET. Mesenchymal cells (a)
adhere to neighboring cells via nectin-based hetero-trans-dimers, which allow accumulation of E-cadherin,
leading to establishment of immature adherens junctions (AJs). These progressively develop into mature AJs
(b), leading to establishment of desmosomes, tight junctions (TJs), and consolidation of apical-basal polarity
(c). Epithelializing cells progressively establish connections with the underlying extracellular matrix (ECM)
through integrin-based cell-matrix junctions (d). The precise order of events is likely to be highly specific to the
cell- and tissue-context, and is reversible in the context of EMT
44
John-Poul Ng-Blichfeldt and Katja Ro ¨ per
developmental and pathological processes. Here, we briefly discuss
the molecular and transcriptional control of MET events that occur
during development, and their implications for cancer metastasis.
2 Making and Breaking Epithelial Junctions
MET involves the stepwise formation of epithelial intercellular
contacts and establishment of apical-basal polarity (Fig. 1). While
the precise order of events is likely to be highly dependent on the
cell- and tissue-context, insight has predominantly come from cell
culture models in which epithelial cells establish apical-basal polarity (reviewed in [3, 4]). An early adhesion event between epithelial
(Àizing) cells is via the transmembrane protein nectin, which forms
calcium-independent hetero-trans-dimers between adjacent cells
[5]. Nectin complexes form scaffolds that recruit the actin-binding
protein afadin, and E-cadherin (CDH1), a prototypical member of
the cadherin family expressed by most epithelial cell types.
E-cadherin forms calcium-dependent homo-trans-dimers with
adjacent cells that progressively mature into AJs and are attached
to the intracellular actin cytoskeleton via alpha- and beta-catenin.
Basal
Apical
ECM
Immature AJ
Mature AJ
Cell-matrix junctions
Desmosome
TJ
Mesenchymal
Epithelial
A)
B)
C)
D)
Fig. 1 Potential mechanisms by which cells establish epithelial junctions during MET. Mesenchymal cells (a)
adhere to neighboring cells via nectin-based hetero-trans-dimers, which allow accumulation of E-cadherin,
leading to establishment of immature adherens junctions (AJs). These progressively develop into mature AJs
(b), leading to establishment of desmosomes, tight junctions (TJs), and consolidation of apical-basal polarity
(c). Epithelializing cells progressively establish connections with the underlying extracellular matrix (ECM)
through integrin-based cell-matrix junctions (d). The precise order of events is likely to be highly specific to the
cell- and tissue-context, and is reversible in the context of EMT
44
John-Poul Ng-Blichfeldt and Katja Ro ¨ per