embryogenesis [27, 28]. GHRL2 also binds to and mediates activation of the CLDN4 gene in renal epithelial cells [61], and
GRHL2 mediates activation of CDH1 and CLDN4 in human
airway epithelium, where it is required for maintenance and establishment of epithelial barrier function [63]. Furthermore, GRHL2
mediates activation of CLDN3 and RAB25 in liver epithelial cells,
which is necessary for translocation of CLDN4 to TJs [64]. Thus,
GRHL TFs may function to maintain the epithelial phenotype in
adult epithelial tissues. Accordingly, GRHL TFs are implicated in a
number of adult human cancers (reviewed in [65]). For example,
GRHL2 is downregulated in mesenchymal (“claudin-low”) primary mammary tumor cells, and ectopic expression is sufficient to
initiate MET in mesenchymal breast cancer cells via binding to the
ZEB1 promoter, mediating its repression, and via induction of
miR-200b/c which inhibits ZEB1 expression [66]. Furthermore,
Table 1
Summary of proposed MET-TFs, and roles in developmental processes described to date
MET-TF
Family members
Developmental processes involved in
References
Grainy-head
family
grh (Drosophila)
GRHL2 controlled neural tube closure in mice
[60]
GRHL1, GRHL2,
GRHL3 (mice and
human)
GRHL2 controlled activation of CDH1 and
CLDN4 in human airway epithelium
[63]
GRHL2 controlled activation of CLDN3 and
RAB25 in mouse liver epithelial cells
[64]
Ovo-like
family
ovo (Drosophila)
OVOL2 restricted EMT in mammary TEB cells in
mice
[70]
OVOL1, OVOL2
(mice and human)
OVOL1/2 controlled basal epidermal
proliferation in mice
[71]
OVOL2 controlled activation of CDH1, RAB25,
and CLDN4 in mouse renal epithelial cysts
in vitro
[62]
OVOL1 controlled kidney and urogenital
development in mice
[62, 73]
Ets-domain
containing
ELF3, ELF5 (mice and
human)
ELF5 restricted EMT in mammary TEB cells in
mice
[77]
ELF3 controlled morphogenesis of intestinal
epithelium in mice
[80]
Singleminded
2
Sim2 (mice and
human)
Sim2 restricted EMT in mammary TEB cells in
mice
[82]
SRY-box 3
Sox3 (mice and
human)
Sox3 repressed Slug to define non-ingressing
ectoderm during chick gastrulation
[83]
50
John-Poul Ng-Blichfeldt and Katja Ro ¨ per
GRHL2 mediates activation of CDH1 and CLDN4 in human
airway epithelium, where it is required for maintenance and establishment of epithelial barrier function [63]. Furthermore, GRHL2
mediates activation of CLDN3 and RAB25 in liver epithelial cells,
which is necessary for translocation of CLDN4 to TJs [64]. Thus,
GRHL TFs may function to maintain the epithelial phenotype in
adult epithelial tissues. Accordingly, GRHL TFs are implicated in a
number of adult human cancers (reviewed in [65]). For example,
GRHL2 is downregulated in mesenchymal (“claudin-low”) primary mammary tumor cells, and ectopic expression is sufficient to
initiate MET in mesenchymal breast cancer cells via binding to the
ZEB1 promoter, mediating its repression, and via induction of
miR-200b/c which inhibits ZEB1 expression [66]. Furthermore,
Table 1
Summary of proposed MET-TFs, and roles in developmental processes described to date
MET-TF
Family members
Developmental processes involved in
References
Grainy-head
family
grh (Drosophila)
GRHL2 controlled neural tube closure in mice
[60]
GRHL1, GRHL2,
GRHL3 (mice and
human)
GRHL2 controlled activation of CDH1 and
CLDN4 in human airway epithelium
[63]
GRHL2 controlled activation of CLDN3 and
RAB25 in mouse liver epithelial cells
[64]
Ovo-like
family
ovo (Drosophila)
OVOL2 restricted EMT in mammary TEB cells in
mice
[70]
OVOL1, OVOL2
(mice and human)
OVOL1/2 controlled basal epidermal
proliferation in mice
[71]
OVOL2 controlled activation of CDH1, RAB25,
and CLDN4 in mouse renal epithelial cysts
in vitro
[62]
OVOL1 controlled kidney and urogenital
development in mice
[62, 73]
Ets-domain
containing
ELF3, ELF5 (mice and
human)
ELF5 restricted EMT in mammary TEB cells in
mice
[77]
ELF3 controlled morphogenesis of intestinal
epithelium in mice
[80]
Singleminded
2
Sim2 (mice and
human)
Sim2 restricted EMT in mammary TEB cells in
mice
[82]
SRY-box 3
Sox3 (mice and
human)
Sox3 repressed Slug to define non-ingressing
ectoderm during chick gastrulation
[83]
50
John-Poul Ng-Blichfeldt and Katja Ro ¨ per