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Lung tumor-associated dendritic cell-derived resistin promoted cancer progression by increasing Wolf-Hirschhorn syndrome candidate 1/Twist pathway.
[wolf-hirschhorn syndrome]
The
interaction
between
tumors
and
their
microenvironments
leads
to
a
vicious
cycle
,
which
strengthens
both
immune
suppression
and
cancer
progression
.
The
present
study
demonstrates
for
the
first
time
that
tumor
-associated
dendritic
cells
(
TADCs
)
are
a
source
of
resistin
,
which
is
responsible
for
increasing
lung
cancer
epithelial-
to
-mesenchymal
transition
.
In
addition
,
large
amounts
of
resistin
in
the
condition
medium
(
CM
)
of
TADCs
increase
cell
migration
and
invasion
,
as
well
as
the
osteolytic
bone
metastatic
properties
of
lung
cancer
cells
.
Neutralization
of
resistin
from
TADC-CM
prevents
the
advanced
malignancy-inducing
features
of
TADC-CM
.
Significantly
elevated
levels
of
resistin
have
been
observed
in
mice
transplanted
with
lung
cancer
cells
,
tumor
-infiltrating
CD
11
c
(
+
)
DCs
in
human
lung
cancer
samples
and
lung
cancer
patients
'
sera
.
Induction
of
lung
cancer
progression
by
TADC-derived
resistin
is
associated
with
increased
expression
of
Wolf-
Hirschhorn
syndrome
candidate
1
(
WHSC
1
)
,
a
histone
methyltransferase
.
Resistin-induced
WHSC
1
increases
the
dimethylation
of
histone
3
at
lysine
36
and
decreases
the
trimethylation
of
histone
3
at
lysine
27
on
the
promoter
of
Twist
,
resulting
in
an
enhancement
of
the
expression
of
Twist
.
Knockdown
of
WHSC
1
by
small
interfering
RNA
transfection
significantly
decreases
resistin
-mediated
cancer
progression
by
decreasing
the
upregulation
of
Twist
,
suggesting
that
WHSC
1
plays
a
critical
role
in
the
regulation
of
Twist
by
epigenetic
modification
.
Furthermore
,
mice
that
received
antiresistin
antibodies
showed
a
decreased
incidence
of
cancer
development
and
metastasis
.
These
findings
suggest
that
TADC-derived
resistin
may
be
a
novel
candidate
in
promoting
the
development
of
lung
cancer
.
Diseases
Validation
Diseases presenting
"lung cancer"
symptom
adrenal incidentaloma
cholangiocarcinoma
cushing syndrome
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
kindler syndrome
liposarcoma
primary effusion lymphoma
severe combined immunodeficiency
systemic capillary leak syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
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