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Laminin-332-integrin interaction: a target for cancer therapy?
[junctional epidermolysis bullosa]
For
many
years
,
extracellular
matrix
(
ECM
)
was
considered
to
function
as
a
tissue
support
and
filler
.
However
,
we
now
know
that
ECM
proteins
control
many
cellular
events
through
their
interaction
with
cell-surface
receptors
and
cytoplasmic
signaling
pathways
.
For
example
,
they
regulate
cell
proliferation
,
cell
division
,
cell
adhesion
,
cell
migration
,
and
apoptosis
.
We
focus
in
this
review
on
a
laminin
isoform
,
laminin-
332
(
formerly
termed
laminin-
5
)
,
a
major
component
of
the
basement
membrane
(
BM
)
of
skin
and
other
epithelial
tissues
.
It
is
composed
of
3
subunits
(
alpha
3
beta
3
and
gamma
3
and
interacts
with
at
least
two
integrin
receptors
expressed
by
epithelial
cells
(
alpha
3
beta
1
and
alpha
6
beta
4
integrin
.
Mutations
in
either
laminin-
332
or
integrin
alpha
6
beta
4
result
in
junctional
epidermolysis
bullosa
,
a
blistering
skin
disease
,
while
targeting
of
laminin-
332
by
autoantibodies
in
cicatricial
pemphigoid
leads
to
dysadhesion
of
epithelial
cells
from
their
underlying
connective
tissue
.
Abnormal
expression
of
laminin-
332
and
its
integrin
receptors
is
also
a
hallmark
of
certain
tumor
types
and
is
believed
to
promote
invasion
of
colon
,
breast
and
skin
cancer
cells
.
Moreover
,
there
is
emerging
evidence
that
laminin-
332
and
its
protease
degradation
products
are
not
only
found
at
the
leading
front
of
several
tumors
but
also
likely
induce
and
/
or
promote
tumor
cell
migration
.
Thus
,
in
this
review
,
we
focus
specifically
on
the
role
of
laminin-
332
and
its
integrin
receptors
in
adhesion
,
proliferation
,
and
migration
/
invasion
of
cancer
cells
.
Finally
,
we
discuss
strategies
for
the
development
of
laminin-
332
-
based
antagonists
for
the
treatment
of
malignant
tumors
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated