Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: July 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.
Development,
Journal Year:
2020,
Volume and Issue:
147(10)
Published: May 15, 2020
ABSTRACT
As
the
crucial
non-cellular
component
of
tissues,
extracellular
matrix
(ECM)
provides
both
physical
support
and
signaling
regulation
to
cells.
Some
ECM
molecules
provide
a
fibrillar
environment
around
cells,
while
others
sheet-like
basement
membrane
scaffold
beneath
epithelial
In
this
Review,
we
focus
on
recent
studies
investigating
mechanical,
biophysical
cues
provided
developing
tissues
by
different
types
in
variety
organisms.
addition,
discuss
how
helps
regulate
tissue
morphology
during
embryonic
development
governing
key
elements
cell
shape,
adhesion,
migration
differentiation.
International Journal of Molecular Sciences,
Journal Year:
2021,
Volume and Issue:
23(1), P. 146 - 146
Published: Dec. 23, 2021
Cancer
progression
with
uncontrolled
tumor
growth,
local
invasion,
and
metastasis
depends
largely
on
the
proteolytic
activity
of
numerous
matrix
metalloproteinases
(MMPs),
which
affect
tissue
integrity,
immune
cell
recruitment,
turnover
by
degrading
extracellular
(ECM)
components
releasing
matrikines,
surface-bound
cytokines,
growth
factors,
or
their
receptors.
Among
MMPs,
MMP-14
is
driving
force
behind
destruction
during
cancer
invasion
metastasis.
also
influences
both
intercellular
as
well
cell-matrix
communication
regulating
many
plasma
membrane-anchored
proteins.
cells
other
stroma,
embedded
in
a
common
matrix,
interact
means
various
adhesive
structures,
particularly
invadopodia
are
capable
to
remodel
through
spatially
temporally
finely
tuned
proteolysis.
As
deeper
understanding
underlying
functional
mechanisms
beneficial
for
development
new
prognostic
predictive
markers
targeted
therapies,
this
review
examined
current
knowledge
interplay
MMPs
context
protein,
subcellular,
cellular
level
focus
MMP14.
Science,
Journal Year:
2022,
Volume and Issue:
376(6594)
Published: May 12, 2022
Understanding
gene
function
and
regulation
in
homeostasis
disease
requires
knowledge
of
the
cellular
tissue
contexts
which
genes
are
expressed.
Here,
we
applied
four
single-nucleus
RNA
sequencing
methods
to
eight
diverse,
archived,
frozen
types
from
16
donors
25
samples,
generating
a
cross-tissue
atlas
209,126
nuclei
profiles,
integrated
across
tissues,
donors,
laboratory
with
conditional
variational
autoencoder.
Using
resulting
atlas,
highlight
shared
tissue-specific
features
tissue-resident
cell
populations;
identify
that
might
contribute
neuromuscular,
metabolic,
immune
components
monogenic
diseases
biological
processes
involved
their
pathology;
determine
modules
underlie
mechanisms
for
complex
traits
analyzed
by
genome-wide
association
studies.
Nature Communications,
Journal Year:
2020,
Volume and Issue:
11(1)
Published: May 15, 2020
Abstract
Chemoresistance
is
a
major
obstacle
in
triple
negative
breast
cancer
(TNBC),
the
most
aggressive
subtype.
Here
we
identify
hypoxia-induced
ECM
re-modeler,
lysyl
oxidase
(LOX)
as
key
inducer
of
chemoresistance
by
developing
chemoresistant
TNBC
tumors
vivo
and
characterizing
their
transcriptomes
RNA-sequencing.
Inhibiting
LOX
reduces
collagen
cross-linking
fibronectin
assembly,
increases
drug
penetration,
downregulates
ITGA5/FN1
expression,
resulting
inhibition
FAK/Src
signaling,
induction
apoptosis
re-sensitization
to
chemotherapy.
Similarly,
inhibiting
results
chemosensitization.
These
effects
are
observed
3D-cultured
cell
lines,
tumor
organoids,
xenografts,
syngeneic
PDX
models.
Re-expressing
hypoxia-repressed
miR-142-3p,
which
targets
HIF1A
,
ITGA5
causes
further
suppression
HIF-1α/LOX/ITGA5/FN1
axis.
Notably,
higher
LOX,
ITGA5,
or
FN1,
lower
miR-142-3p
levels
associated
with
shorter
survival
chemotherapy-treated
patients.
provide
strong
pre-clinical
rationale
for
testing
inhibitors
overcome
