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The tumor suppressive role of NUMB isoform 1 in esophageal squamous cell carcinoma.
[esophageal carcinoma]
Esophageal
quamous
cell
carcinoma
(
ESCC
)
is
the
predominant
histological
type
of
esophageal
carcinoma
in
Asian
populations
.
To
date
,
few
biomarkers
have
been
identified
for
ESCC
.
In
present
study
,
we
found
a
tumor
suppressor
,
NUMB
isoform
1
(
NUMB
-
1
)
,
as
a
promising
prognostic
biomarker
for
patients
with
ESCC
.
NUMB
-
1
mRNA
was
downregulated
in
66
.
7
%
of
primary
ESCC
tissues
when
compared
with
matched
adjacent
non-
tumor
tissues
.
The
low
expression
of
NUMB
-
1
was
significantly
associated
with
high
tumor
recurrence
(
p
=
0
.
029
)
and
poor
post-operative
overall
survival
(
p
=
0
.
016
)
.
To
further
explore
the
underlying
mechanisms
by
which
NUMB
-
1
regulates
ESCC
,
we
demonstrated
that
ectopic
expression
of
NUMB
-
1
inhibited
cell
proliferation
through
inducing
G
2
/
M
phase
arrest
,
which
was
accompanied
by
an
increase
in
p
21
and
cyclin
B
1
-
cdc
2
levels
.
However
,
it
had
no
impact
on
apoptosis
of
ESCC
cells
.
In
addition
,
overexpression
of
NUMB
-
1
prevented
epithelial-mesenchymal
transition
,
inhibited
invasion
of
ESCC
cells
and
NOTCH
pathway
,
suppressed
Aurora
-
A
activity
by
preventing
phosphorylation
of
Aurora
-
A
at
T
288
which
resulted
in
cell
cycle
arrest
.
Taken
together
,
our
findings
suggested
NUMB
-
1
functions
as
a
tumor
-suppressor
and
serves
as
a
prognositc
biomarker
for
ESCC
patients
;
thus
,
NUMB
-
1
may
be
a
potential
novel
therapeutic
target
for
treatment
of
ESCC
.
Diseases
Validation
Diseases presenting
"poor post-operative overall survival"
symptom
esophageal carcinoma
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