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Ganoderiol A-enriched extract suppresses migration and adhesion of MDA-MB-231 cells by inhibiting FAK-SRC-paxillin cascade pathway.
[wiskott-aldrich syndrome]
Cell
adhesion
,
migration
and
invasion
are
critical
steps
for
carcinogenesis
and
cancer
metastasis
.
Ganoderma
lucidum
,
also
called
Lingzhi
in
China
,
is
a
traditional
Chinese
medicine
,
which
exhibits
anti-proliferation
,
anti-
inflammation
and
anti-metastasis
properties
.
Herein
,
GAEE
,
G
.
lucidum
extract
mainly
contains
ganoderiol
A
(
GA
)
,
dihydrogenated
GA
and
GA
isomer
,
was
shown
to
inhibit
the
abilities
of
adhesion
and
migration
,
while
have
a
slight
influence
on
that
of
invasion
in
highly
metastatic
breast
cancer
MDA-
MB
-
231
cells
at
non-toxic
doses
.
Further
investigation
revealed
that
GAEE
decreased
the
active
forms
of
focal
adhesion
kinase
(
FAK
)
and
disrupted
the
interaction
between
FAK
and
SRC
,
which
lead
to
deactivating
of
paxillin
.
Moreover
,
GAEE
treatment
downregulated
the
expressions
of
RhoA
,
Rac
1
,
and
Cdc
42
,
and
decreased
the
interaction
between
neural
Wiskott-
Aldrich
Syndrome
protein
(
N-WASP
)
and
Cdc
42
,
which
impair
cell
migration
and
actin
assembly
.
To
our
knowledge
,
this
is
the
first
report
to
show
that
G
.
lucidum
triterpenoids
could
suppress
cell
migration
and
adhesion
through
FAK-
SRC
-
paxillin
signaling
pathway
.
Our
study
also
suggests
that
GAEE
may
be
a
potential
agent
for
treatment
of
breast
cancer
.
Diseases
Validation
Diseases presenting
"highly metastatic breast cancer"
symptom
wiskott-aldrich syndrome
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