International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(8), С. 4283 - 4283
Опубликована: Апрель 12, 2024
Sialyltransferase-catalyzed
membrane
protein
and
lipid
glycosylation
plays
a
vital
role
as
one
of
the
most
abundant
post-translational
modifications
diversification
reactions
in
eukaryotes.
However,
aberrant
sialylation
has
been
associated
with
cancer
malignancy
metastasis.
Sialyltransferases
thus
represent
emerging
targets
for
development
small
molecule
drugs.
Herein,
we
report
inhibitory
effects
recently
discovered
lithocholic
acid
derivative
FCW393
on
sialyltransferase
catalytic
activity,
integrin
sialyation,
cancer-associated
signal
transduction,
MDA-MB-231
B16F10
cell
migration
invasion,
vivo
studies,
tumor
growth,
metastasis,
angiogenesis.
showed
effective
selective
inhibition
sialyltransferases
ST6GAL1
(IC50
=
7.8
μM)
ST3GAL3
9.45
relative
to
ST3GAL1
>
400
ST8SIA4
100
μM).
reduced
breast
melanoma
cells
dose-dependently
downregulated
proteins
integrin-regulated
FAK/paxillin
GEF/Rho/ROCK
pathways,
VEGF-regulated
Akt/NFκB/HIF-1α
pathway.
inhibited
2.6
invasion
vitro
experiments,
studies
tumor-bearing
mice,
size,
angiogenesis,
metastatic
potential.
Based
its
demonstrated
selectivity,
permeability,
relatively
low
cytotoxicity
55
μM),
high
efficacy,
shows
promising
potential
experimental
tool
compound
lead
further
novel
therapeutic.
Journal of Biomolecular NMR,
Год журнала:
2023,
Номер
77(3), С. 111 - 119
Опубликована: Июнь 1, 2023
Abstract
In
the
last
three
decades,
scope
of
solid-state
NMR
has
expanded
to
exploring
complex
biomolecules,
from
large
protein
assemblies
intact
cells
at
atomic-level
resolution.
This
diversity
in
macromolecules
frequently
features
highly
flexible
components
whose
insoluble
environment
precludes
use
solution
study
their
structure
and
interactions.
While
High-resolution
Magic-Angle
Spinning
(HR-MAS)
probes
offer
capacity
for
gradient-based
1
H-detected
spectroscopy
solids,
such
are
not
commonly
used
routine
MAS
experiments.
As
a
result,
most
exploration
regime
entails
either
13
C-detected
experiments,
partially
perdeuterated
systems,
or
ultra-fast
MAS.
Here
we
explore
proton-detected
pulse
schemes
probing
through-bond
C–
C
networks
mobile
sidechains
as
well
polysaccharides
broadband
manner.
We
demonstrate
mixture
microtubule-associated
(MAP)
tau
human
microtubules
(MTs),
cell
wall
fungus
Schizophyllum
commune
using
2D
3D
spectroscopy,
show
its
viability
obtaining
unambiguous
correlations
standard
fast-spinning
high
ultra-high
magnetic
fields.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Окт. 24, 2024
Recurrent
breast
cancers
often
develop
resistance
to
standard-of-care
therapies.
Identifying
targetable
factors
contributing
cancer
recurrence
remains
the
rate-limiting
step
in
improving
long-term
outcomes.
In
this
study,
we
identify
tumor
cell-derived
osteopontin
as
an
autocrine
and
paracrine
driver
of
recurrence.
Osteopontin
promotes
cell
proliferation,
recruits
macrophages,
synergizes
with
IL-4
further
polarize
them
into
a
pro-tumorigenic
state.
Macrophage
depletion
inhibition
decrease
recurrent
growth.
Furthermore,
targeting
primary
tumor-bearing
female
mice
prevents
metastasis,
permits
T
infiltration
activation,
improves
anti-PD-1
immunotherapy
response.
Clinically,
expression
is
higher
metastatic
tumors
versus
patient-matched
tumors.
positively
correlates
macrophage
infiltration,
increases
grade,
its
elevated
pathway
activity
associated
poor
prognosis
Our
findings
suggest
clinical
implications
alternative
therapeutic
strategy
based
on
osteopontin's
multiaxial
role
progression
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Янв. 26, 2025
Abstract
Oral
submucous
fibrosis
(OSF)
is
a
chronic,
progressive,
and
fibrotic
condition
of
the
oral
mucosa
that
carries
an
elevated
risk
malignant
transformation.
We
aimed
to
identify
validate
novel
genes
associated
with
regulation
epithelial-to-mesenchymal
transition
(EMT)
in
OSF.
Genes
regulating
EMT
were
identified
through
differential
gene
expression
analysis,
using
LogFC
threshold
-1
+
1
padj
value
<
0.05,
based
on
data
from
GEO
datasets
TCGA-HNSC
datasets.
The
curated
correlated
functional
cancer
states
subjected
clustering
candidate
genes.
Integration
bioinformatics
proteomics
led
discovery
MMP9
,
SPARC
ITGA5
as
candidates.
Comprehensive
pathway
immunohistochemical
analyses
confirmed
their
roles
OSF,
squamous
cell
carcinoma
(OSCC),
OSF-associated
(OSFSCC).
significant
malignancy
suggest
mechanism
which
fibrosis-associated
type
2
undergoes
3
EMT,
driving
OSF
towards
malignancy.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(5), С. 1798 - 1798
Опубликована: Фев. 20, 2025
Cancer
is
the
second
most
common
cause
of
death
in
world,
representing
one
main
economic
burdens
health
care
and
research.
The
effort
research
has
mainly
focused
on
limiting
growth
a
localized
tumor,
but
recently,
there
been
more
attention
restricting
spreading
cancer
via
invasion
metastasis.
signaling
pathways
behind
these
two
processes
share
many
molecules
with
physiological
regulating
cell
adhesion
migration,
and,
moreover,
migration
themselves
underlie
tumor
potential
for
invasion.
In
this
work,
we
reviewed
latest
literature
about
development
their
regulation
by
migration-
adhesion-related
proteins,
specific
focus
talins
integrins.
We
also
summarized
recent
developments
approaches
to
anti-cancer
therapies,
concentrating
migration-related
therapies.
Frontiers in Cell and Developmental Biology,
Год журнала:
2025,
Номер
13
Опубликована: Март 18, 2025
The
mechanical
properties
of
the
tumor
microenvironment
(TME)
undergo
significant
changes
during
growth,
primarily
driven
by
alterations
in
extracellular
(ECM)
stiffness
and
viscoelasticity.
These
not
only
promote
progression
but
also
hinder
therapeutic
efficacy
impairing
drug
delivery
activating
mechanotransduction
pathways
that
regulate
crucial
cellular
processes
such
as
migration,
proliferation,
resistance
to
therapy.
In
this
review,
we
examine
mechanisms
through
which
cells
sense
transmit
signals
maintain
homeostasis
biomechanically
altered
TME.
We
explore
current
computational
modelling
strategies
for
pathways,
highlighting
need
developing
models
incorporate
additional
components
mechanosignaling
machinery.
Furthermore,
review
available
methods
measuring
tumors
clinical
settings
aiming
at
restoring
TME
blocking
deregulated
pathways.
Finally,
propose
proper
characterization
a
deeper
understanding
landscape
TME,
both
tissue
levels,
are
essential
account
influence
forces
on
treatment
efficacy.
International Journal of Translational Medicine,
Год журнала:
2022,
Номер
2(3), С. 419 - 447
Опубликована: Авг. 19, 2022
Despite
significant
advances
in
the
understanding
of
cancer
biology,
is
still
a
leading
cause
death
worldwide.
Expression
tumor
microenvironment
component,
osteopontin,
tissues,
plasma,
and
serum,
has
been
shown
to
be
associated
with
poor
prognosis
survival
rate
various
human
cancers.
Recent
studies
suggest
that
osteopontin
drives
development
aggressiveness
using
strategies.
In
this
review,
we
first
provide
an
overview
how
promotes
progression,
such
as
growth,
invasion,
angiogenesis,
immune
modulation,
well
metastasis
chemoresistance.
Next,
address
functional
activities
are
modulated
by
interaction
integrins
CD44
receptors,
but
also
post-translational
modification,
proteolytic
processing
several
proteases,
phosphorylation,
glycosylation.
Then,
review
activates
tumor-associated
macrophages
(TAMs)
cancer-associated
fibroblasts
(CAFs),
functions
immunosuppressor
regulating
surveillance
checkpoint
microenvironment.
Finally,
discuss
potential
applications
biomarker
therapeutic
target.
Annals of the Rheumatic Diseases,
Год журнала:
2023,
Номер
82(11), С. 1474 - 1486
Опубликована: Июль 21, 2023
Activation
of
fibroblasts
is
a
hallmark
fibrotic
processes.
Besides
cytokines
and
growth
factors,
are
regulated
by
the
extracellular
matrix
environment
through
receptors
such
as
integrins,
which
transduce
biochemical
mechanical
signals
enabling
cells
to
mount
appropriate
responses
according
biological
demands.
The
aim
this
work
was
investigate
in
vivo
role
collagen-fibroblast
interactions
for
regulating
fibroblast
functions
fibrosis.Triple
knockout
(tKO)
mice
with
combined
ablation
integrins
α1β1,
α2β1
α11β1
were
created
address
significance
integrin-mediated
cell-collagen
communication.
Properties
primary
dermal
lacking
collagen-binding
delineated
vitro.
Response
tKO
skin
bleomycin
induced
challenge
assessed.Triple
integrin-deficient
develop
normally,
transiently
smaller
reveal
mild
alterations
mechanoresilience
skin.
Fibroblasts
from
these
culture
show
defects
cytoskeletal
architecture,
traction
stress
generation,
production
organisation.
Ablation
three
leads
increased
levels
discoidin
domain
receptor
2,
an
alternative
recognising
collagens
However,
overexpression
fails
compensate
adhesion
spreading
on
collagen
substrates
Mice
severely
attenuated
response
impaired
mechanotransduction,
reduced
organisation.The
data
provide
evidence
crucial
force
generation
differentiation
vitro
deposition
tissue
remodelling
vivo.
Targeting
fibroblast-collagen
might
represent
promising
therapeutic
approach
regulate
connective
diseases.