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Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways.
[kallmann syndrome]
Anosmin-
1
,
encoded
by
the
KAL
1
gene
,
is
an
extracellular
matrix
(
ECM
)
-
associated
protein
which
plays
essential
roles
in
the
establishment
of
olfactory
and
GNRH
neurons
during
early
brain
development
.
Loss
-of-function
mutations
of
KAL
1
results
in
Kallmann
syndrome
with
delayed
puberty
and
anosmia
.
There
is
,
however
,
little
comprehension
of
its
role
in
the
developed
brain
.
As
reactivation
of
developmental
signal
pathways
often
takes
part
in
tumorigenesis
,
we
investigated
if
anosmin-
1
-
mediated
cellular
mechanisms
associated
with
brain
tumors
.
Our
meta
-analysis
of
gene
expression
profiles
of
patients
'
samples
and
public
microarray
datasets
indicated
that
KAL
1
mRNA
was
significantly
upregulated
in
high
-grade
primary
brain
tumors
compared
with
the
normal
brain
and
low
-grade
tumors
.
The
tumor
-promoting
capacity
of
anosmin-
1
was
demonstrated
in
the
glioblastoma
cell
lines
,
where
anosmin-
1
enhanced
cell
motility
and
proliferation
.
Notably
,
anosmin-
1
formed
a
part
of
active
β
1
integrin
complex
,
inducing
downstream
signaling
pathways
.
ShRNA-mediated
knockdown
of
anosmin-
1
attenuated
motility
and
growth
of
tumor
cells
and
induced
apoptosis
.
Anosmin-
1
may
also
enhance
the
invasion
of
tumor
cells
within
the
ECM
by
modulating
cell
adhesion
and
activating
extracellular
proteases
.
In
a
mouse
xenograft
model
,
anosmin-
1
-
expressing
tumors
grew
faster
,
indicating
the
role
of
anosmin-
1
in
tumor
microenvironment
in
vivo
.
Combined
,
these
data
suggest
that
anosmin-
1
can
facilitate
tumor
cell
proliferation
,
migration
,
invasion
,
and
survival
.
Therefore
,
although
the
normal
function
of
anosmin-
1
is
required
in
the
proper
development
of
GNRH
neurons
,
overexpression
of
anosmin-
1
in
the
developed
brain
may
be
an
underlying
mechanism
for
some
brain
tumors
.
Diseases
Validation
Diseases presenting
"early brain development"
symptom
kallmann syndrome
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