The epipliancy journey: Tumor initiation at the mercy of identity crisis and epigenetic drift
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer,
Год журнала:
2025,
Номер
1880(3), С. 189307 - 189307
Опубликована: Апрель 2, 2025
Cellular
pliancy
refers
to
the
unique
disposition
of
different
stages
cellular
differentiation
transform
when
exposed
specific
oncogenic
insults.
This
concept
highlights
a
strong
interconnection
between
identity
and
tumorigenesis,
implies
overcoming
epigenetic
barriers
defining
states.
Emerging
evidence
suggests
that
cell-type-specific
response
intrinsic
extrinsic
stresses
is
modulated
by
accessibility
certain
areas
genome.
Understanding
interplay
mechanisms,
differentiation,
insults
crucial
for
deciphering
complex
nature
tumorigenesis
developing
targeted
therapies.
Hence,
relies
on
dynamic
cooperation
context
through
control,
including
reactivation
such
as
epithelial-to-mesenchymal
transition
(EMT).
Such
mechanisms
pathways
confer
plasticity
cell
allowing
it
adapt
hostile
environment
in
tumor
initiation,
thus
changing
its
identity.
Indeed,
growing
cancer
disease
crisis,
whereby
differentiated
cells
lose
their
defined
gain
progenitor
characteristics.
The
loss
fate
commitment
central
feature
appears
be
prerequisite
neoplastic
transformation.
In
this
context,
EMT-inducing
transcription
factors
(EMT-TFs)
cooperate
with
mitogenic
oncoproteins
foster
malignant
aberrant
activation
EMT-TFs
plays
an
active
role
initiation
alleviating
key
oncosuppressive
endowing
stem
cell-like
properties,
ability
self-renew,
course
tumorigenesis.
highly
phenotypic
change
occurs
concomitantly
major
epigenome
reorganization,
component
regulation.
was
initially
proposed
address
fundamental
question
biology:
why
are
some
more
likely
become
cancerous
events
at
particular
developmental
stages?
We
propose
epipliancy,
difference
configuration
leads
transformation
following
insult.
Here,
we
present
recent
studies
furthering
our
understanding
how
landscape
may
impact
modulation
during
early
initiation.
Язык: Английский
The Clinical Relevance of Epithelial-to-Mesenchymal Transition Hallmarks: A Cut-Off-Based Approach in Healthy and Cancerous Cell Lines
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(8), С. 3617 - 3617
Опубликована: Апрель 11, 2025
The
atypical
activation
of
the
epithelial-to-mesenchymal
transition
represents
one
main
mechanisms
driving
cancer
cell
dissemination.
It
enables
epithelial
cells
to
detach
from
primary
tumor
mass
and
gain
survival
advantages
in
bloodstream,
significantly
contributing
spread
circulating
cells.
Notably,
is
not
a
binary
process
but
rather
leads
formation
wide
range
subpopulations
characterized
by
simultaneous
expression
both
mesenchymal
markers.
Therefore,
analyzing
modulation
EMT
hallmarks
during
conversion
healthy
metastatic
cells,
which
acquire
stem
characteristics,
particular
interest.
This
study
investigates
panel
transition-related
genes
lines,
derived
various
tissues,
including
lung,
colon,
pancreas,
skin,
neuro-ectoderm,
with
aim
identifying
potential
cut-off
values
for
assessing
aggressiveness.
Interestingly,
we
found
that
levels
CDH1,
encodes
marker
E-cadherin,
CDH5,
encoding
vascular
endothelial
cadherin,
transition-transcription
factor
ZEB1,
effectively
distinguished
Additionally,
our
data
suggest
tissue-specific
signature
markers
progression.
Overall,
results
underscore
importance
investigating
as
identify
most
suitable
acting
indicators
disease
aggressiveness
therapeutic
responsiveness.
Язык: Английский
Recurring cycles of deprivation of serum and migration in confined spaces augments ganglioside SSEA-4 expression, boosting clonogenicity and cisplatin resistance in TNBC cell line
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Май 14, 2025
Abstract
The
remarkable
biophysical
properties
of
metastatic
migrating
cells,
such
as
their
exceptional
motility
and
deformability,
enable
them
to
migrate
through
physical
confinements
created
by
neighboring
cells
or
extracellular
matrix.
This
study
explores
the
adaptive
responses
breast
cancer
(BC)
cell
sublines
derived
from
highly
aggressive,
triple-negative
MDA-MB-231
non-metastatic
MCF7
human
BC
lines,
after
undergoing
three
rounds
confined
migration
(CM)
stress.
Our
findings
demonstrate
that
CM
elicits
common
cell-type
specific
in
sublines.
In
particular,
both
exhibit
a
similar
enhancement
clonogenicity
nanoparticle
(NP)
uptake
activity,
indicating
tumorigenic
potential.
We
have,
for
first
time,
shown
stimulation
with
induces
hybrid
epithelial-to-mesenchymal
transition
(EMT)
phenotype
cells.
is
characterized
significant
rise
expression
stage-specific
embryonic
antigen-4
(SSEA4),
alongside
substantial
decline
population
CD133+
marked
reduction
Ki67
MDA-MB-231-derived
subline
following
Cis-Platin
treatment.
These
changes
are
likely
associated
heightened
resistance
this
cisplatin.
contrast,
far
fewer
alterations
MCF7-derived
counterpart
notable
increase
population,
which
seems
be
insufficient
change
susceptibility
cisplatin
exposure.
contributes
our
understanding
mechanisms
underlying
metastasis
drug
cancer,
emphasizing
need
personalized
approaches
treatment
consider
heterogeneous
different
subtypes
environmental
stresses.
Язык: Английский
Gene regulatory network transitions reveal the central transcription factors in lung adenocarcinoma progression
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Май 14, 2025
Abstract
Transcription
factors
play
a
central
role
in
cancer
growth,
progression,
and
metastasis,
contribute
to
intratumor
phenotypic
plasticity
which
enable
drug
tolerance
relapse.
Changes
the
regulatory
activities
of
transcription
may
not
always
be
detected
by
investigating
mutational
signatures
or
differential
expression
factor,
as
done
traditional
analysis.
In
addition,
past
studies
have
focused
on
tumors
whole
thus,
fully
captured
heterogeneity
gene
regulation
among
different
cell
types
within
tumor
microenvironment.
this
work,
through
an
analysis
transitions
network
architecture
dynamics,
we
identify
associated
with
lung
adenocarcinoma
progression.
The
NR2F1
,
neurodevelopment
dormancy,
emerge
key
factor
progression
adenocarcinoma.
We
further
that
are
only
active
samples
uncover
how
changes
dynamics
influence
heterogeneity.
Taken
together,
our
work
elucidates
during
identifies
process,
reveals
complex
cooccurring
Язык: Английский
Prognostic Significance of Combining Cytokeratin-19, E-Cadherin and Ki-67 Analysis in Triple-Negative Breast Cancer with Basal-Like and Non-Basal-Like Phenotype
Zahra Klayech,
A. Moussa,
Moufida Souid
и другие.
Cancer Investigation,
Год журнала:
2024,
Номер
42(9), С. 769 - 781
Опубликована: Окт. 20, 2024
Triple-negative
breast
cancer
(TNBC)
is
known
to
have
the
worst
outcome
compared
other
forms
of
cancer.
Moreover,
molecular
markers
identified
basal-like
(BLBC)
phenotypes
be
also
related
a
worse
prognosis.
In
this
study,
we
evaluated
by
immunohistochemistry
(IHC)
prognostic
significance
combining
Cytokeratin-19
(CK19),
E-cadherin,
and
Ki-67
tissue
expression
in
triple-negative
cases
presenting
or
non-basal-like
(n-BLBC)
phenotype
improve
selection
monitoring
BC
patients
with
more
aggressive
outcome.
Herein,
when
n-BLBC,
BLBC
showed
positive
correlation
lymph
node
metastasis
occurrence
lower
survival
rates.
Immunohistochemistry
analysis
revealed
significantly
E-cadherin
prevalence
higher
both
CK19
n-BLBC.
Spearman
that
negatively
correlated
expressions.
BLBC,
expressing
combined
loss
was
associated
relapse-free
overall
survival.
conclusion,
TNBC/BLBC
simultaneously
losing
overexpressing
are
most
forms.
This
could
predictive
marker
poor
Язык: Английский
GABA Type A receptors expressed in triple negative breast cancer cells mediate chloride ion flux
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Окт. 14, 2024
Triple
negative
breast
cancer
(TNBC)
is
known
for
its
heterogeneous
nature
and
aggressive
onset,
limited
unresponsiveness
to
hormone
therapies
immunotherapy
as
well
high
likelihood
of
metastasis
recurrence.
Since
no
targeted
standard
treatment
options
are
available
TNBC,
novel
effective
therapeutic
targets
urgently
needed.
Ion
channels
have
emerged
possible
candidates
therapy.
We
previously
showed
that
GABA
A
β3
subunit
expressed
at
higher
levels
in
TNBC
cell
lines
than
non-tumorigenic
MCF10A
cells.
knockdown
causes
cycle
arrest
via
decreased
cyclin
D1
increased
p21
expression.
However,
it
not
if
the
upregulated
R
express
cell-surface
mediate
Cl
−
flux.
ions
play
a
role
cell-cycle
progression
other
cancers
such
gastric
cancer.
Here,
using
surface
biotinylation
(N-(Ethoxycarbonylmethyl)-6-Methoxyquinolinium
Bromide)
MQAE-dye
based
fluorescence
quenching,
we
show
on
significantly
chloride
(Cl
)
flux
compared
Moreover,
this
mediated
can
be
modulated
by
pharmacological
agents
cells
with
knockdown.
Further,
bicuculline,
antagonist
reduced
viability
Overall,
these
results
point
an
unexplored
TNBC.
Язык: Английский