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Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2.
[esophageal squamous cell carcinoma]
Stat
3
alters
the
expression
of
its
downstream
genes
and
is
associated
with
tumor
invasion
and
metastasis
in
several
human
cancers
.
Its
role
in
esophageal
squamous
cell
carcinoma
(
ESCC
)
has
not
been
well
characterized
.
We
examined
the
tumor
sections
of
100
cases
of
ESCC
by
immunohistochemistry
and
observed
significant
overexpression
of
Stat
3
in
the
cytoplasm
of
89
Â
%
of
ESCC
cells
and
of
phosphorylated
Stat
3
(
p
-
Stat
3
)
in
the
nuclei
of
71
Â
%
of
ESCC
when
compare
with
normal
esophageal
mucosa
(
72
Â
%
,
p
Â
=
Â
0
.
02
;
and
31
Â
%
,
p
Â
=
Â
0
.
001
)
.
Overexpression
of
Stat
3
and
p
-
Stat
3
positively
correlated
with
that
of
matrix
metalloproteinase-
2
(
MMP
2
)
,
a
known
regulator
for
cell
migration
,
in
65
Â
%
of
ESCC
while
only
26
Â
%
shown
in
benign
esophageal
mucosa
.
To
further
investigate
the
association
of
Stat
3
with
tumor
metastasis
in
vitro
,
invasion
of
EC
-
1
cells
(
a
human
ESCC
cell
line
)
were
investigated
with
Boyden
chambers
.
The
results
showed
that
transfection
of
Stat
3
not
only
promoted
invasion
of
EC
-
1
cells
but
also
significantly
induced
MMP
2
expression
in
a
dose-dependent
manner
.
In
contrast
,
suppressing
expression
of
endogenous
Stat
3
mRNA
and
protein
by
Stat
3
siRNA
significantly
reduced
EC
-
1
cell
invasion
and
MMP
2
expression
.
A
high
-affinity
Stat
3
-
binding
element
was
localized
to
the
positions
of
648
-
641
Â
bp
(
TTCTCGAA
)
in
the
MMP
2
promoter
with
electrophoretic
mobility
shift
assay
.
Our
results
suggest
that
Stat
3
,
p
-
Stat
3
,
and
MMP
2
were
overexpressed
in
ESCC
and
associated
with
invasion
of
ESCC
;
and
Stat
3
up-regulated
expression
of
MMP
2
in
ESCC
through
directly
binding
to
the
MMP
2
promoter
.
