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Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous cell carcinoma.
[esophageal squamous cell carcinoma]
Esophageal
squamous
cell
carcinoma
(
ESCC
)
is
one
of
the
most
common
malignancies
in
Asia
.
Currently
,
surgical
resection
of
early
stage
tumor
is
the
best
available
treatment
.
However
,
most
patients
present
late
when
surgery
is
not
an
option
.
Data
suggests
that
chemotherapy
regimens
are
inadequate
for
clinical
management
of
advanced
cancer
.
Targeted
therapy
has
emerged
as
one
of
the
most
promising
approaches
to
treat
several
malignancies
.
A
pre-requisite
for
developing
targeted
therapy
is
prior
knowledge
of
proteins
and
pathways
that
drive
proliferation
in
malignancies
.
We
carried
out
phosphotyrosine
profiling
across
four
different
ESCC
cell
lines
and
compared
it
to
non-neoplastic
Het
1
A
cell
line
to
identify
activated
tyrosine
kinase
signaling
pathways
in
ESCC
.
A
total
of
278
unique
phosphopeptides
were
identified
across
these
cell
lines
.
This
included
several
tyrosine
kinases
and
their
substrates
that
were
hyperphosphorylated
in
ESCC
.
Ephrin
receptor
A
2
(
EPHA
2
)
,
a
receptor
tyrosine
kinase
was
hyperphosphorylated
in
all
the
ESCC
cell
lines
used
in
the
study
.
EPHA
2
is
reported
to
be
oncogenic
in
several
cancers
and
is
also
known
to
promote
metastasis
.
Immunohistochemistry
based
studies
have
revealed
EPHA
2
is
overexpressed
in
nearly
50
%
of
ESCC
.
We
demonstrate
EPHA
2
as
a
potential
therapeutic
target
in
ESCC
by
carrying
out
siRNA
based
knockdown
studies
.
Knockdown
of
EPHA
2
in
ESCC
cell
line
TE
8
resulted
in
significant
decrease
in
cell
proliferation
and
invasion
suggesting
it
is
a
promising
therapeutic
target
in
ESCC
that
warrants
further
evaluation
.
This
article
is
protected
by
copyright
.
All
rights
reserved
.
Diseases
Validation
Diseases presenting
"advanced cancer"
symptom
cholangiocarcinoma
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
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