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c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
[liposarcoma]
Genomic
amplification
of
the
c-
Jun
proto-oncogene
has
been
identified
in
∼
30
%
of
dedifferentiated
liposarcomas
(
DDLPS
)
,
but
the
functional
contribution
of
c-
Jun
to
the
progression
of
DDLPS
remains
poorly
understood
.
In
previous
work
we
showed
that
knock-down
of
c-
Jun
by
RNA
interference
impaired
the
in
vitro
proliferation
and
in
vivo
growth
of
a
DDLPS
cell
line
(
LP
6
)
with
genomic
amplification
of
the
c-
Jun
locus
.
Here
,
we
used
gene
expression
analysis
and
functional
studies
in
a
broad
panel
of
cell
lines
to
further
define
the
role
of
c-
Jun
in
DDLPS
and
other
soft
tissue
sarcomas
.
We
show
that
c-
Jun
knock-down
impairs
transition
through
the
G
1
phase
of
the
cell
cycle
in
multiple
DDLPS
cell
lines
.
We
also
found
that
high
levels
of
c-
Jun
expression
are
both
necessary
and
sufficient
to
promote
DDLPS
cell
migration
and
invasion
in
vitro
.
Our
data
suggest
that
high
levels
of
c-
Jun
enhance
motility
in
part
by
driving
the
expression
of
ENPP
2
/
Autotaxin
.
c-
Jun
over-expression
has
minimal
effects
on
in
vitro
proliferation
but
substantially
enhances
the
in
vivo
growth
of
weakly
tumourigenic
DDLPS
cell
lines
.
Finally
,
we
provide
evidence
that
c-
Jun
genomic
amplification
and
over-expression
may
have
similar
functional
consequences
in
other
types
of
soft
tissue
sarcoma
.
Our
data
suggest
a
model
in
which
relatively
low
levels
of
c-
Jun
are
sufficient
for
in
vitro
proliferation
,
but
high
levels
of
c-
Jun
enhance
invasiveness
and
capacity
for
in
vivo
tumour
growth
.
These
observations
provide
an
explanation
for
the
selective
advantage
provided
by
c-
Jun
genomic
amplification
in
vivo
and
suggest
that
sarcomas
with
elevated
c-
Jun
levels
are
likely
to
have
a
particularly
high
malignant
potential
.
Data
from
exon
array
and
RNA-Seq
experiments
have
been
deposited
in
the
GEO
database
(
Accession
No
.
GSE
57531
)
.
Diseases
Validation
Diseases presenting
"functional studies in a broad panel"
symptom
liposarcoma
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