Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Фев. 5, 2025
Metastasis
in
cancer
is
influenced
by
epigenetic
factors.
Using
an
vivo
screen,
we
demonstrate
that
several
subunits
of
the
polybromo-associated
BAF
(PBAF)
chromatin
remodeling
complex,
particularly
Brd7,
are
required
for
maintaining
breast
metastatic
dormancy
lungs
female
mice.
Brd7
loss
induces
reawakening,
along
with
modifications
epigenomic
landscapes
and
upregulated
oncogenic
signaling.
Breast
cells
harboring
inactivation
also
reprogram
surrounding
immune
microenvironment
downregulating
MHC-1
expression
promoting
a
pro-metastatic
cytokine
profile.
Flow
cytometric
single-cell
analyses
reveal
increased
levels
pro-tumorigenic
inflammatory
transitional
neutrophils,
CD8+
exhausted
T
cells,
CD4+
stress
response
from
mice
Brd7-deficient
metastases.
Finally,
attenuating
this
immunosuppressive
milieu
neutrophil
depletion,
extracellular
trap
(NET)
inhibition,
or
checkpoint
therapy
abrogates
outgrowth.
These
findings
implicate
PBAF
triggering
outgrowth
cancer,
pointing
to
targetable
underlying
mechanisms
involving
specific
cell
compartments.
Metastasis-initiating
can
reawaken
dormant
state
initially
allowed
them
survive,
Here,
authors
show
promotes
tumor
drives
reawakening
lung.
Cell,
Год журнала:
2023,
Номер
186(19), С. 4007 - 4037
Опубликована: Сен. 1, 2023
The
TGF-β
regulatory
system
plays
crucial
roles
in
the
preservation
of
organismal
integrity.
signaling
controls
metazoan
embryo
development,
tissue
homeostasis,
and
injury
repair
through
coordinated
effects
on
cell
proliferation,
phenotypic
plasticity,
migration,
metabolic
adaptation,
immune
surveillance
multiple
types
shared
ecosystems.
Defects
signaling,
particularly
epithelial
cells,
fibroblasts,
disrupt
tolerance,
promote
inflammation,
underlie
pathogenesis
fibrosis
cancer,
contribute
to
resistance
these
diseases
treatment.
Here,
we
review
how
coordinates
multicellular
response
programs
health
disease
this
knowledge
can
be
leveraged
develop
treatments
for
system.
Distant
metastasis
remains
the
major
cause
of
morbidity
for
breast
cancer.
Individuals
with
liver
or
brain
have
an
extremely
poor
prognosis
and
low
response
rates
to
anti-PD-1/L1
immune
checkpoint
therapy
compared
those
at
other
sites.
Therefore,
it
is
urgent
investigate
underlying
mechanism
resistance
develop
more
effective
immunotherapy
strategies
these
patients.
Using
single-cell
RNA
sequencing,
a
high-resolution
map
entire
tumor
ecosystem
based
on
44
473
cells
from
cancer
metastases
depicted.
Identified
by
canonical
markers
confirmed
multiplex
immunofluorescent
staining,
metastatic
features
remarkable
reprogramming
immunosuppressive
such
as
FOXP3+
regulatory
T
cells,
LAMP3+
tolerogenic
dendritic
CCL18+
M2-like
macrophages,
RGS5+
cancer-associated
fibroblasts,
LGALS1+
microglial
cells.
In
addition,
PD-1
PD-L1/2
are
barely
expressed
in
CD8+
cancer/immune/stromal
respectively.
Interactions
molecules
LAG3-LGALS3
TIGIT-NECTIN2
between
found
play
dominant
roles
escape.
summary,
this
study
dissects
intratumoral
heterogeneity
microenvironment
first
time,
providing
insights
into
most
appropriate
Clinical and Translational Medicine,
Год журнала:
2022,
Номер
12(2)
Опубликована: Фев. 1, 2022
Abstract
Background
Deciphering
intra‐
and
inter‐tumoural
heterogeneity
is
essential
for
understanding
the
biology
of
gastric
cancer
(GC)
its
metastasis
identifying
effective
therapeutic
targets.
However,
characteristics
different
organ‐tropism
metastases
GC
are
largely
unknown.
Methods
Ten
fresh
human
tissue
samples
from
six
patients,
including
primary
tumour
adjacent
non‐tumoural
organs
or
tissues
(liver,
peritoneum,
ovary,
lymph
node)
were
evaluated
using
single‐cell
RNA
sequencing.
Validation
experiments
performed
histological
assays
bulk
transcriptomic
datasets.
Results
Malignant
epithelial
subclusters
associated
with
invasion
features,
intraperitoneal
propensity,
epithelial–mesenchymal
transition‐induced
stem
cell
phenotypes,
dormancy‐like
discovered.
High
expression
first
three
subcluster‐associated
genes
displayed
worse
overall
survival
than
those
low
in
a
cohort
containing
407
samples.
Immune
stromal
cells
exhibited
cellular
created
pro‐tumoural
immunosuppressive
microenvironment.
Furthermore,
20‐gene
signature
node‐derived
exhausted
CD8
+
T
was
acquired
to
forecast
node
validated
cohorts.
Additionally,
although
anti‐NKG2A
(KLRC1)
antibody
have
not
been
used
treat
patients
even
clinical
trials,
we
uncovered
only
malignant
but
one
endothelial
subcluster,
mucosal‐associated
invariant
cells,
cell‐like
B
plasmacytoid
dendritic
macrophages,
monocytes,
neutrophils
may
contribute
HLA‐E‐KLRC1/KLRC2
interaction
cytotoxic/exhausted
and/or
natural
killer
(NK)
suggesting
novel
opportunities
GC.
our
findings
suggested
that
PD‐1
might
predict
responses
blockade
therapy
Conclusions
This
study
provided
insights
into
heterogeneous
microenvironment
tumours
organ‐specific
provide
support
precise
diagnosis
treatment.
Seminars in Cancer Biology,
Год журнала:
2022,
Номер
86, С. 136 - 145
Опубликована: Сен. 29, 2022
TGF-β
plays
a
prominent
role
as
an
inducer
of
epithelial-mesenchymal
transitions
(EMTs)
during
development
and
wound
healing
in
disease
conditions
such
fibrosis
cancer.
During
these
processes
EMT
occurs
together
with
changes
cell
proliferation,
differentiation,
communication,
extracellular
matrix
remodeling
that
are
orchestrated
by
multiple
signaling
inputs
besides
TGF-β.
Chief
among
is
RAS-MAPK
signaling,
which
frequently
required
for
induction
Recent
work
elucidated
the
molecular
basis
cooperation
between
TGF-β-SMAD
pathways
embryonic,
adult
carcinoma
epithelial
cells.
These
studies
also
provided
direct
mechanistic
links
progenitor
differentiation
gastrulation
or
intra-tumoral
cancer
metastasis.
insights
illuminate
nature
driven
EMTs
part
broader
development,
fibrogenesis
