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Role of the focal adhesion protein kindlin-1 in breast cancer growth and lung metastasis.
[kindler syndrome]
Fermitin
family
member
1
(
FERMT
1
,
Kindlin-
1
)
is
an
epithelial-
specific
regulator
of
integrin
functions
and
is
associated
with
Kindler
syndrome
,
a
genetic
disorder
characterized
by
skin
blistering
,
atrophy
,
and
photosensitivity
.
However
,
the
possible
role
of
kindlin-
1
in
cancer
remains
unknown
.
Kindlin-
1
expression
was
quantified
in
several
human
cancers
using
quantitative
real-time
polymerase
chain
reaction
and
published
microarray
datasets
.
The
association
between
kindlin-
1
expression
and
patient
metastasis-free
survival
(
N
=
516
)
was
assessed
with
Kaplan-
Meier
analyses
.
Effects
of
ectopic
expression
or
silencing
of
kindlin-
1
on
cell
signaling
,
migration
,
and
invasion
were
assessed
in
human
breast
cancer
cell
lines
using
western
blotting
,
immunofluorescence
,
wound
healing
assays
,
and
invasion
on
Matrigel
or
type
I
collagen
substrates
.
Breast
tumor
growth
and
lung
metastasis
were
evaluated
in
12
-
week
-old
female
BALB
/
c
mice
(
10
controls
and
six
Kindlin-
1
-
knockdown
mice
)
.
All
statistical
tests
were
two
-sided
.
Kindlin-
1
expression
was
consistently
higher
in
tumors
than
in
normal
tissues
in
various
cancer
types
metastasizing
to
the
lungs
,
including
colon
and
bladder
cancer
.
Kindlin-
1
expression
was
associated
with
metastasis-free
survival
in
both
breast
and
lung
adenocarcinoma
(
breast
cancer
:
hazard
ratio
of
lung
metastasis
=
2
.
55
,
95
%
confidence
intervals
[
CI
]
=
1
.
39
to
4
.
69
,
P
=
.
001
;
lung
cancer
:
hazard
ratio
of
metastasis
=
1
.
96
,
95
%
CI
=
1
.
25
to
3
.
07
,
P
=
.
001
)
.
Overexpression
of
kindlin-
1
induced
changes
indicating
epithelial-mesenchymal
transition
and
transforming
growth
factor
beta
(
TGF
β
)
signaling
,
constitutive
activation
of
cell
motility
,
and
invasion
(
number
of
migrating
cells
,
Kindlin-
1
cells
vs
control
,
mean
=
164
.
66
vs
.
19
.
00
,
difference
=
145
.
6
,
95
%
CI
=
79
.
1
to
212
.
2
,
P
=
.
004
;
invasion
rate
,
Kindlin-
1
-
cells
vs
control
=
9
.
65
%
vs
.
1
.
92
%
,
difference
=
7
.
73
%
,
95
%
CI
=
4
.
75
to
10
.
70
,
P
<
.
001
)
.
Finally
,
Kindlin-
1
depletion
in
an
orthotopic
mouse
model
statistically
significantly
inhibited
breast
tumor
growth
(
P
<
.
001
)
and
lung
metastasis
(
P
=
.
003
)
.
These
results
suggest
a
role
for
kindlin-
1
in
breast
cancer
lung
metastasis
and
lung
tumorigenesis
and
advance
our
understanding
of
kindlin-
1
as
a
regulator
of
TGF
β
signaling
,
offering
new
avenues
for
therapeutic
intervention
against
cancer
progression
.
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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