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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
"large amounts"
symptom
canavan disease
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
fabry disease
omenn syndrome
oral submucous fibrosis
papillon-lefèvre syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
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