Increased prevalence of hybrid epithelial/mesenchymal state and enhanced phenotypic heterogeneity in basal breast cancer
iScience,
Год журнала:
2024,
Номер
27(7), С. 110116 - 110116
Опубликована: Май 27, 2024
Highlights•Luminal
signature
is
closely
associated
with
epithelial
in
breast
cancer•Basal
correlates
well
a
hybrid
epithelial-mesenchymal
signature•Basal
cancer
exhibits
higher
heterogeneity
patterns•Mathematical
modeling
of
underlying
gene
networks
explains
observed
heterogeneitySummaryIntra-tumoral
phenotypic
promotes
tumor
relapse
and
therapeutic
resistance
remains
an
unsolved
clinical
challenge.
Decoding
the
interconnections
among
different
biological
axes
plasticity
crucial
to
understand
molecular
origins
heterogeneity.
Here,
we
use
multi-modal
transcriptomic
data—bulk,
single-cell,
spatial
transcriptomics—from
cell
lines
primary
samples,
identify
associations
between
transition
(EMT)
luminal-basal
plasticity—two
key
processes
that
enable
We
show
luminal
strongly
associates
state,
but
basal
epithelial/mesenchymal
phenotype(s)
Mathematical
core
regulatory
representative
crosstalk
elucidate
mechanistic
underpinnings
from
data.
Our
systems-based
approach
integrating
data
analysis
mechanism-based
offers
predictive
framework
characterize
intra-tumor
interventions
restrict
it.Graphical
abstract
Язык: Английский
Shared mechanisms for metastasis and drug resistance in prostate cancer
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer,
Год журнала:
2025,
Номер
1880(4), С. 189358 - 189358
Опубликована: Май 28, 2025
Язык: Английский
Advance in prostate cancer biomarker discovery: bridging detection, prognosis and therapeutics
Discover Oncology,
Год журнала:
2025,
Номер
16(1)
Опубликована: Май 30, 2025
Язык: Английский
A synthetic lethal screen for Snail-induced enzalutamide resistance identifies JAK/STAT signaling as a therapeutic vulnerability in prostate cancer
Frontiers in Molecular Biosciences,
Год журнала:
2023,
Номер
10
Опубликована: Май 9, 2023
Despite
substantial
improvements
in
the
treatment
landscape
of
prostate
cancer,
evolution
hormone
therapy-resistant
and
metastatic
cancer
remains
a
major
cause
cancer-related
death
globally.
The
mainstay
for
advanced
is
targeting
androgen
receptor
signaling,
including
deprivation
therapy
plus
second-generation
blockade
(e.g.,
enzalutamide,
apalutamide,
darolutamide),
and/or
synthesis
inhibition
(abiraterone).
While
these
agents
have
significantly
prolonged
lives
patients
with
nearly
universal.
This
resistance
mediated
by
diverse
mechanisms,
both
receptor-dependent
such
as
mutations,
amplifications,
alternative
splicing,
amplification,
well
non-androgen
receptor-mediated
lineage
plasticity
toward
neuroendocrine-like
or
epithelial-mesenchymal
transition
(EMT)-like
lineages.
Our
prior
work
identified
EMT
transcriptional
regulator
Snail
critical
to
hormonal
commonly
detected
human
cancer.
In
current
study,
we
sought
interrogate
actionable
EMT-mediated
resistant
identify
synthetic
lethality
collateral
sensitivity
approaches
treating
this
aggressive,
disease
state.
Using
combination
high-throughput
drug
screens
multi-parameter
phenotyping
confluence
imaging,
ATP
production,
phenotypic
reporters
EMT,
candidate
lethalities
Snail-mediated
These
analyses
multiple
targets,
XPO1,
PI3K/mTOR,
aurora
kinases,
c-MET,
polo-like
JAK/STAT
Snail+
We
validated
targets
subsequent
validation
screen
an
LNCaP-derived
model
sequential
enzalutamide.
follow-up
provided
inhibitors
PI3K/mTOR
therapeutic
vulnerabilities
enzalutamide-resistant
Язык: Английский
Establishment and characterization of the gemcitabine-resistant human gallbladder cancer cell line NOZ GemR
Annals of Medicine and Surgery,
Год журнала:
2024,
Номер
86(3), С. 1396 - 1400
Опубликована: Янв. 3, 2024
Background:
Patients
with
gallbladder
cancer
(GBC)
generally
receive
gemcitabine
as
the
standard
treatment;
however,
its
efficacy
is
often
limited
owing
to
development
of
resistance.
Methods:
To
identify
mechanisms
underlying
resistance
in
GBC,
a
gemcitabine-resistant
GBC
cell
line
(NOZ
GemR)
was
established
by
exposing
parental
NOZ
increasing
concentrations
gemcitabine.
Morphological
changes,
growth
rates,
and
migratory
invasive
capabilities
were
evaluated.
Protein
expression
detected
using
western
blotting.
Results:
The
results
demonstrated
that
IC
50
GemR
0.011
4.464
μM,
respectively,
index
ratio
405.8.
In
comparison,
cells
grew
slower
had
significantly
lower
migration
invasion
abilities
than
cells.
There
altered
levels
epithelial-mesenchymal
transformation
markers
cells,
well
increased
Akt/mTOR
pathway
protein.
Conclusion:
could
be
used
an
effective
vitro
model
improve
our
understanding
GBC.
Язык: Английский
Multi-modal transcriptomic analysis unravels enrichment of hybrid epithelial/mesenchymal state and enhanced phenotypic heterogeneity in basal breast cancer
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Окт. 2, 2023
Intra-tumoral
phenotypic
heterogeneity
promotes
tumor
relapse
and
therapeutic
resistance
remains
an
unsolved
clinical
challenge.
It
manifests
along
multiple
axes
decoding
the
interconnections
among
these
different
is
crucial
to
understand
its
molecular
origins
develop
novel
strategies
control
it.
Here,
we
use
multi-modal
transcriptomic
data
analysis
-
bulk,
single-cell
spatial
transcriptomics
from
breast
cancer
cell
lines
primary
samples,
identify
associations
between
epithelial-mesenchymal
transition
(EMT)
luminal-basal
plasticity
two
key
processes
that
enable
heterogeneity.
We
show
luminal
strongly
associates
with
epithelial
state,
but
basal
associated
hybrid
epithelial/mesenchymal
phenotype(s)
higher
These
patterns
were
inherent
in
methylation
profiles,
suggesting
epigenetic
crosstalk
EMT
lineage
cancer.
Mathematical
modelling
of
core
underlying
gene
regulatory
networks
representative
recapitulate
thus
elucidate
mechanistic
underpinnings
observed
data.
Our
systems-based
approach
integrating
mechanism-based
modeling
offers
a
predictive
framework
characterize
intra-tumor
possible
interventions
restrict
Язык: Английский