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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
"published microarray datasets"
symptom
kindler syndrome
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