Exposomal determinants of non-genetic plasticity in tumor initiation
Trends in cancer,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Unraveling the YAP1-TGFβ1 axis: a key driver of androgen receptor loss in prostate cancer-associated fibroblasts
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 1, 2025
Abstract
Due
to
their
pivotal
roles
in
tumor
progression
and
therapy
resistance,
cancer-associated
fibroblasts
(CAF)
are
considered
key
therapeutic
targets
with
loss
of
stromal
androgen
receptor
(AR)
a
poorly
understood
hallmark
aggressive
prostate
cancer
(PCa).
A
paucity
pre-clinical
models
however
has
hampered
functional
studies
CAF
heterogeneity.
We
demonstrate
that
our
newly-generated
biobank
contains
three
FAP
+
-fibroblast
subtypes,
each
unique
molecular
traits.
Cultures
an
early-activated
phenotype
expressed
the
highest
levels
AR
exhibited
AR-dependent
growth.
Consistently,
cells
expressing
early-activation
markers
co-expressed
nuclear
clinical
specimens
were
enriched
pre-neoplastic
lesions/low-grade
PCa.
Conversely,
myofibroblastic
(myCAF),
which
low
vitro
vivo
proliferatively-insensitive
signaling
modulation,
constituted
predominant
subpopulation
stromogenic
high-grade
PCa
castration-resistant
LACP9
patient-derived
xenografts.
Exacerbation
myCAF
state
upon
castration
LAPC9-bearing
hosts
underscored
these
findings.
Mechanistically,
was
driven
by
NFκB-TGFβ1-YAP1
axis,
whose
combined
targeting
synergistically
repressed
hallmarks
impaired
autophagic
flux,
effects
potentiated
enzalutamide
resulting
cell
death.
Collectively,
findings
provide
mechanistic
rationale
for
adjuvant
YAP1-TGFβ
axis
improve
patient
outcomes.
Язык: Английский
Mapping Tumor–Stroma–ECM Interactions in Spatially Advanced 3D Models of Pancreatic Cancer
ACS Applied Materials & Interfaces,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 7, 2025
Bioengineering-based
in
vitro
tumor
models
are
increasingly
important
as
tools
for
studying
disease
progression
and
therapy
response
many
cancers,
including
the
deadly
pancreatic
ductal
adenocarcinoma
(PDAC)
that
exhibits
a
tumor/tissue
microenvironment
of
high
cellular/biochemical
complexity.
Therefore,
it
is
crucial
to
capture
complexity
enable
investigation
interplay
between
cancer
cells
factors
such
extracellular
matrix
(ECM)
proteins
or
stroma
cells.
Using
polyurethane
(PU)
scaffolds,
we
performed
systematic
study
on
how
different
ECM
protein
scaffold
coatings
impact
long-term
cell
evolution
scaffolds
containing
only
(activated
stellate
endothelial
cells).
To
investigate
potential
further
changes
those
biomarkers
due
cancer-stroma
interactions,
mapped
their
expression
dual/zonal
consisting
core
periphery,
spatially
mimicking
fibrotic/desmoplastic
reaction
PDAC.
In
our
single
observed
coating
affected
spatial
aggregation,
deposition,
biomarker
upregulation
cell-line-dependent
manner.
levels
fibrosis/desmoplasia
terms
composition/quantity
were
generated
depending
coating.
When
model,
linked
aggressiveness/invasiveness
upregulated
by
both
compared
models.
Collectively,
advances
understanding
PU
scaffolds.
Our
findings
show
within
bioengineered
models,
can
stimulate
PDAC
develop
aggressiveness/invasiveness,
well
fibrosis.
Furthermore,
highlight
importance
considering
map
invasion.
work
contributes
design
with
variable,
yet
biomimetic,
tissue-like
properties
microenvironment's
role
progression.
Язык: Английский
Mechanistic role of stromal cancer-associated fibroblasts in tumorigenesis and brain metastasis: highlighting drug resistance and targeted therapy
Pathology - Research and Practice,
Год журнала:
2025,
Номер
unknown, С. 155918 - 155918
Опубликована: Март 1, 2025
Язык: Английский
Emodin Decreases Tumor-Associated Macrophages Accumulation and Suppresses Bladder Cancer Development by Inhibiting CXCL1 Secretion from Cancer-Associated Fibroblasts
Nutrition and Cancer,
Год журнала:
2025,
Номер
unknown, С. 1 - 16
Опубликована: Март 20, 2025
Tumor-associated
macrophages
(TAMs)
and
cancer-associated
fibroblasts
(CAFs)
are
the
most
abundant
stromal
cells
in
bladder
cancer
(BC)
microenvironment
(TME).
However,
detailed
mechanisms
underlying
TAM-CAF
communication
their
contributions
to
BC
progression
remain
incompletely
understood.
Emerging
evidence
shows
that
Emodin
exerts
anti-tumor
effect
on
several
tumor
models
by
targeting
TME.
To
date,
impact
of
has
not
been
previously
reported.
Our
study
firstly
demonstrated
significantly
inhibited
growth
reduced
TAM
accumulation
a
murine
model.
markedly
decreased
serum
levels
multiple
chemokines
tumor-bearing
mice,
with
CXCL1
showing
pronounced
reduction.
Strikingly,
selectively
suppressed
secretion
CAFs
but
TAMs
or
cells.
Furthermore,
decrease
migration
induced
was
dependent
CAF-derived
CXCL1.
Using
subcutaneous
model,
we
found
failed
inhibit
when
CXCL1-deficient
were
co-injected
cells,
underscoring
critical
role
this
process.
Bioinformatics
analysis
further
revealed
elevated
correlated
negatively
invasive/metastatic
potential
overall
survival
patients.
In
conclusion,
our
findings
establish
delays
disrupting
CXCL1-mediated
crosstalk
between
TAMs.
Язык: Английский
Multidimensional transcriptomics based to illuminate the mechanisms of taurine metabolism in immune resistance of pancreatic cancer
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Март 31, 2025
Pancreatic
cancer,
a
highly
malignant
tumor
of
the
digestive
system,
is
characterized
by
microenvironment
with
high
degree
immunosuppression.
This
immunosuppressive
property
poses
significant
challenges,
as
it
hampers
effective
infiltration
immune
cells
and
impairs
their
ability
to
exert
cytotoxic
effects.
The
metabolic
process
taurine
has
emerged
crucial
factor
in
modulating
functions
activities
cells.
Intervening
metabolism
holds
potential
reshape
microenvironment,
thereby
enhancing
recognize
eliminate
To
explore
therapeutic
relationship
between
disorders
pancreatic
cancer
immunotherapy,
we
employed
multiple
software
packages,
including
"Seurat",
"DoubletFinder",
"Harmony",
"GSVA",
"CellChat"
analyze
single-cell
data
spatial
transcriptomic
cancer.
In
present
study,
four
distinct
cell
subsets,
namely
RPS4Y1+
cells,
LYZ+
CPE+
MKI67+
were
identified
for
first
time.
CNV
score
highlighted
role
within
Through
cell-communication
analysis,
crosstalk
among
fibroblasts,
CD8+
T
was
identified,
offering
novel
insights
into
immunotherapy
strategies,
which
strengthened
co-localization
analysis
transcriptomics.
Furthermore,
conducting
combined
survival
data,
LY6D
target.
co-culture
experiments
uncovered
underlying
mechanism
regulating
imbalance
establishment
"taurine-immune
crosstalk"
criteria
this
study
effectively
paves
way
immunotherapy.
conclusion,
current
research
underscores
significance
Targeting
may
represent
approach
reversing
"stiff-cancer"
characteristics
Язык: Английский
Exosomal circRNAs: key modulators in breast cancer progression
Cell Death Discovery,
Год журнала:
2025,
Номер
11(1)
Опубликована: Апрель 24, 2025
Abstract
Breast
cancer
(BC)
poses
significant
challenges
globally,
necessitating
a
deeper
understanding
of
its
complexities.
Exosomes
are
cell-specific
secreted
extracellular
vesicles
interest,
characterized
by
lipid
bilayer
structure.
can
carry
variety
bioactive
components,
including
nucleic
acids,
lipids,
amino
and
small
molecules,
to
mediate
intercellular
signaling.
CircRNAs
novel
class
single-stranded
RNA
closed-loop
mainly
exert
ceRNA
functions
intricately
modulate
gene
expression
signaling
pathways
in
breast
cancer,
influencing
tumor
progression
therapeutic
responses.
The
unique
packaging
circRNAs
within
exosomes
serves
as
genetic
information
transmitters,
facilitating
communication
between
BC
cells
microenvironmental
cells,
thereby
regulating
critical
aspects
progression,
immune
evasion,
drug
resistance.
Besides,
exosomal
possess
the
capabilities
serving
diagnostic
biomarkers
BC,
due
their
stability,
specificity,
regulatory
roles
tumorigenesis
metastasis.
Therefore,
this
review
aims
elucidate
mechanisms
well
potential
for
diagnosis
therapeutics.
ongoing
investigations
will
potentially
revolutionize
treatment
paradigms
improve
patient
outcomes
BC.
Язык: Английский