Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Июль 31, 2023
Abstract
Cellular
mechanotransduction,
a
critical
regulator
of
numerous
biological
processes,
is
the
conversion
from
mechanical
signals
to
biochemical
regarding
cell
activities
and
metabolism.
Typical
cues
in
organisms
include
hydrostatic
pressure,
fluid
shear
stress,
tensile
force,
extracellular
matrix
stiffness
or
tissue
elasticity,
viscosity.
Mechanotransduction
has
been
expected
trigger
multiple
such
as
embryonic
development,
repair
regeneration.
However,
prolonged
excessive
stimulation
can
result
pathological
multi-organ
fibrosis,
tumorigenesis,
cancer
immunotherapy
resistance.
Although
associations
between
normal
homeostasis
diseases
have
identified,
regulatory
mechanisms
among
different
are
not
yet
comprehensively
illustrated,
no
effective
therapies
currently
available
targeting
cue-related
signaling.
This
review
systematically
summarizes
characteristics
typical
conditions
with
updated
evidence.
The
key
effectors
responding
stimulations
listed,
Piezo
channels,
integrins,
Yes-associated
protein
(YAP)
/transcriptional
coactivator
PDZ-binding
motif
(TAZ),
transient
receptor
potential
vanilloid
4
(TRPV4).
We
also
reviewed
signaling
pathways,
therapeutic
targets
cutting-edge
clinical
applications
related
cues.
Nature reviews. Cancer,
Год журнала:
2020,
Номер
20(3), С. 174 - 186
Опубликована: Янв. 24, 2020
Abstract
Cancer-associated
fibroblasts
(CAFs)
are
a
key
component
of
the
tumour
microenvironment
with
diverse
functions,
including
matrix
deposition
and
remodelling,
extensive
reciprocal
signalling
interactions
cancer
cells
crosstalk
infiltrating
leukocytes.
As
such,
they
potential
target
for
optimizing
therapeutic
strategies
against
cancer.
However,
many
challenges
present
in
ongoing
attempts
to
modulate
CAFs
benefit.
These
include
limitations
our
understanding
origin
heterogeneity
CAF
function,
it
being
desirable
retain
some
antitumorigenic
functions.
On
basis
meeting
experts
field
biology,
we
summarize
this
Consensus
Statement
current
knowledge
framework
advancing
critical
cell
type
within
microenvironment.
Frontiers in Molecular Biosciences,
Год журнала:
2020,
Номер
6
Опубликована: Янв. 30, 2020
Solid
tumors
are
complex
organ-like
structures
that
consist
not
only
of
tumor
cells
but
also
vasculature,
extracellular
matrix
(ECM),
stromal
and
immune
cells.
Often
this
microenvironment
(TME),
comprises
the
larger
part
overall
mass.
Like
other
components
TME
ECM
in
solid
differs
significantly
from
normal
organs.
Intratumoral
signaling,
transport
mechanisms,
metabolisms,
oxygenation,
immunogenicity
strongly
affected
if
controlled
by
ECM.
Exerting
regulatory
control,
does
influence
malignancy
growth
its
response
towards
therapy.
Understanding
particularities
is
necessary
to
develop
approaches
interfere
with
negative
effect.
In
review,
we
will
highlight
current
understanding
physical,
cellular
molecular
mechanisms
which
pathological
affects
efficiency
radio-,
chemo-
immunotherapy.
Finally,
discuss
various
strategies
target
modify
how
they
could
be
utilized
improve
FEBS Journal,
Год журнала:
2021,
Номер
288(24), С. 6850 - 6912
Опубликована: Фев. 21, 2021
Extracellular
matrix
(ECM)
is
a
dynamic
3‐dimensional
network
of
macromolecules
that
provides
structural
support
for
the
cells
and
tissues.
Accumulated
knowledge
clearly
demonstrated
over
last
decade
ECM
plays
key
regulatory
roles
since
it
orchestrates
cell
signaling,
functions,
properties
morphology.
Extracellularly
secreted
as
well
cell‐bound
factors
are
among
major
members
family.
Proteins/glycoproteins,
such
collagens,
elastin,
laminins
tenascins,
proteoglycans
glycosaminoglycans,
hyaluronan,
their
receptors
CD44
integrins,
responsible
adhesion,
comprise
well‐organized
functional
with
significant
in
health
disease.
On
other
hand,
enzymes
metalloproteinases
specific
glycosidases
including
heparanase
hyaluronidases
contribute
to
remodeling
affect
human
health.
Several
processes
them
proliferation
survival,
migration,
differentiation,
autophagy,
angiogenesis,
immunity
regulation
affected
by
certain
components.
Structural
alterations
have
been
also
associated
disease
progression.
This
guide
on
composition
functions
gives
broad
overview
matrisome,
macromolecules,
interaction
networks
within
surface,
summarizes
main
features
tissue
organization
emphasizes
importance
constituents
development
progression
advances
molecular
targeting
design
new
therapeutic
strategies.
The
role
of
the
physical
microenvironment
in
tumor
development,
progression,
metastasis,
and
treatment
is
gaining
appreciation.
emerging
multidisciplinary
field
sciences
cancer
now
embraced
by
engineers,
physicists,
cell
biologists,
developmental
oncologists
attempting
to
understand
how
parameters
processes
affect
progression
treatment.
Discoveries
this
are
starting
be
translated
into
new
therapeutic
strategies
for
cancer.
In
Review,
we
propose
four
traits
tumors
that
contribute
resistance:
(i)
elevated
solid
stresses
(compression
tension),
(ii)
interstitial
fluid
pressure,
(iii)
altered
material
properties
(for
example,
increased
tissue
stiffness,
which
historically
has
been
used
detect
palpation),
(iv)
microarchitecture.
After
defining
these
traits,
discuss
their
causes,
consequences,
they
complement
biological
hallmarks
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Янв. 2, 2023
Abstract
Integrins
are
considered
the
main
cell-adhesion
transmembrane
receptors
that
play
multifaceted
roles
as
extracellular
matrix
(ECM)-cytoskeletal
linkers
and
transducers
in
biochemical
mechanical
signals
between
cells
their
environment
a
wide
range
of
states
health
diseases.
Integrin
functions
dependable
on
delicate
balance
active
inactive
status
via
multiple
mechanisms,
including
protein-protein
interactions,
conformational
changes,
trafficking.
Due
to
exposure
cell
surface
sensitivity
molecular
blockade,
integrins
have
been
investigated
pharmacological
targets
for
nearly
40
years,
but
given
complexity
sometimes
opposite
characteristics,
targeting
integrin
therapeutics
has
challenge.
To
date,
only
seven
drugs
successfully
marketed,
abciximab,
eptifibatide,
tirofiban,
natalizumab,
vedolizumab,
lifitegrast,
carotegrast.
Currently,
there
approximately
90
kinds
integrin-based
therapeutic
or
imaging
agents
clinical
studies,
small
molecules,
antibodies,
synthetic
mimic
peptides,
antibody–drug
conjugates
(ADCs),
chimeric
antigen
receptor
(CAR)
T-cell
therapy,
agents,
etc.
A
serious
lesson
from
past
drug
discovery
research
efforts
is
successes
rely
both
deep
understanding
integrin-regulatory
mechanisms
unmet
needs.
Herein,
we
provide
systematic
complete
review
all
family
members
integrin-mediated
downstream
signal
transduction
highlight
ongoing
develop
new
therapies/diagnoses
bench
clinic.
In
addition,
further
discuss
trend
development,
how
improve
success
rate
trials
therapies,
key
points
research,
basic
translational
research.
The
nucleus
makes
the
rules
Single
cells
continuously
experience
and
react
to
mechanical
challenges
in
three-dimensional
tissues.
Spatial
constraints
dense
tissues,
physical
activity,
injury
all
impose
changes
cell
shape.
How
can
measure
shape
deformations
ensure
correct
tissue
development
homeostasis
remains
largely
unknown
(see
Perspective
by
Shen
Niethammer).
Working
independently,
Venturini
et
al.
Lomakin
now
show
that
act
as
an
intracellular
ruler
cellular
variations.
nuclear
envelope
provides
a
gauge
of
deformation
activates
mechanotransduction
pathway
controls
actomyosin
contractility
migration
plasticity.
thereby
allows
adapt
their
behavior
local
microenvironment.
Science
,
this
issue
p.
eaba2644
eaba2894
;
see
also
295
