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The MUC1 mucin regulates the tumorigenic properties of human esophageal adenocarcinomatous cells.
[esophageal adenocarcinoma]
MUC
1
is
a
membrane-bound
mucin
known
to
participate
in
tumor
proliferation
.
It
has
been
shown
that
MUC
1
pattern
of
expression
is
modified
during
esophageal
carcinogenesis
,
with
a
progressive
increase
from
metaplasia
to
adenocarcinoma
.
The
principal
cause
of
development
of
esophageal
adenocarcinoma
is
gastro-
esophageal
reflux
and
MUC
1
was
previously
shown
to
be
up-regulated
by
several
bile
acids
present
in
reflux
.
In
this
report
,
our
aim
was
thus
to
determine
whether
MUC
1
plays
a
role
in
biological
properties
of
human
esophageal
cancer
cells
.
For
that
,
a
stable
MUC
1
-
deficient
esophageal
cancer
cell
line
was
established
using
a
shRNA
approach
.
In
vitro
(
proliferation
,
migration
and
invasion
)
and
in
vivo
(
tumor
growth
following
subcutaneous
xenografts
in
SCID
mice
)
biological
properties
of
MUC
1
-
deficient
cells
were
analyzed
.
Our
results
show
that
esophageal
cancer
cells
lacking
MUC
1
were
less
proliferative
and
had
decreased
migration
and
invasion
properties
.
These
alterations
were
accompanied
by
a
decreased
activity
of
NFKB
p
65
,
Akt
and
MAPK
(
p
44
/
42
,
JNK
and
p
38
)
pathways
.
MCM
6
and
TSG
101
tumor
-associated
markers
were
also
decreased
.
Subcutaneous
xenografts
showed
a
significant
decrease
in
tumor
size
when
cells
did
not
express
MUC
1
.
Altogether
,
the
data
indicate
that
MUC
1
plays
a
key
role
in
proliferative
,
migrating
and
invasive
properties
of
esophageal
cancer
cells
as
well
as
in
tumor
growth
promotion
.
MUC
1
mucin
appears
thus
as
a
good
therapeutic
target
to
slow
down
esophageal
tumor
progression
.
Diseases
Validation
Diseases presenting
"deficient cells"
symptom
child syndrome
esophageal adenocarcinoma
gm1 gangliosidosis
junctional epidermolysis bullosa
kindler syndrome
lymphangioleiomyomatosis
neonatal adrenoleukodystrophy
werner syndrome
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