PLoS ONE,
Год журнала:
2024,
Номер
19(12), С. e0316476 - e0316476
Опубликована: Дек. 31, 2024
Background
Gastric
cancer
(GC)
is
a
highly
malignant
gastrointestinal
tumor
characterized
by
difficult
early
diagnosis
and
poor
prognosis.
Therefore,
it
imperative
to
explore
potential
therapeutic
targets
for
gastric
cancer.
PARP9
abnormally
expressed
in
variety
of
tumors
associated
with
cell
apoptosis
DNA
damage.
However,
its
relationship
GC
has
not
been
fully
studied.
Methods
The
expression
prognostic
significance
were
examined
using
bioinformatics
approaches.
Cell
lines
either
knockdown
or
overexpression
established
through
lentiviral
transduction,
the
role
phenotypes
cells
was
validated
via
CCK8
assays,
wound
healing
clonogenic
Transwell
migration
experiments.
Finally,
alterations
downstream
signaling
pathways
following
changes
analyzed
RNA
sequencing.
Results
tissues
can
significantly
inhibit
proliferation,
invasion
cells,
increase
damage
cells.
process
may
be
realized
synergistic
interaction
SOX6
MAPK
pathway.
Conclusions
Our
study
reveals
link
between
GC,
providing
new
target
treatment
GC.
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
174, С. 116574 - 116574
Опубликована: Апрель 8, 2024
Gastrointestinal
(GI)
cancer
is
one
of
the
most
severe
types
cancer,
with
a
significant
impact
on
human
health
worldwide.
Due
to
urgent
demand
for
more
effective
therapeutic
strategies
against
GI
cancers,
novel
research
metal
ions
treating
cancers
has
attracted
increasing
attention.
Currently,
accumulating
relationship
between
and
therapy,
several
have
been
discovered
induce
cell
death.
In
particular,
three
modes
death,
including
ferroptosis,
cuproptosis,
calcicoptosis,
become
focal
points
in
field
cancer.
Meanwhile,
other
also
found
trigger
death
through
various
mechanisms.
Accordingly,
this
review
focuses
mechanisms
ion-induced
hoping
provide
theoretical
support
further
therapies.
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Апрель 22, 2024
Abstract
Distant
metastasis
is
a
significant
hallmark
affecting
to
the
high
death
rate
of
patients
with
triple-negative
breast
cancer
(TNBC).
Thus,
it
crucial
identify
and
develop
new
therapeutic
strategies
hinder
metastasis.
While
emerging
studies
have
hinted
pivotal
role
glucose-regulated
protein
94
(GRP94)
in
tumorigenesis,
exact
biological
functions
molecular
mechanisms
GRP94
modulating
remain
be
elucidated.
Our
study
demonstrated
an
increased
expression
TNBC
correlated
metastatic
progression
unfavorable
prognosis
patients.
Functionally,
we
identified
that
depletion
significantly
diminished
tumorigenesis
subsequent
lung
In
contrast,
overexpression
exacerbated
invasiveness,
migration,
non-TNBC
cells.
Mechanistically,
found
casein
kinase
2
alpha
(CK2α)
active
advanced
phosphorylated
at
conserved
serine
306
(S306)
residue.
This
phosphorylation
stability
enhanced
its
interaction
LRP6,
leading
activation
canonical
Wnt
signaling.
From
standpoint,
benzamidine,
novel
CK2α
inhibitor,
effectively
suppressed
phosphorylation,
LRP6
stabilization,
TNBC.
results
point
critical
CK2α-mediated
through
signaling,
highlighting
as
target
impede
Cell Death and Disease,
Год журнала:
2025,
Номер
16(1)
Опубликована: Янв. 18, 2025
Abstract
The
aberrant
upregulation
of
Yes-associated
protein
1
(YAP1)
in
a
variety
solid
cancers
contributes
to
tumor
progression
and
poor
clinical
outcomes,
rendering
it
an
appealing
therapeutic
target.
However,
effective
therapies
directly
target
YAP1
remain
challenging.
In
this
study,
we
perform
high-throughput
screening
identify
Casein
kinase
II
(CK2)
as
uncharacterized
upstream
regulator
turnover
cancer
cells
ovarian
several
other
types.
Pharmacological
inhibition
by
Silmitasertib
or
genetic
depletion
the
catalytic
subunit
(CK2α)
markedly
destabilizes
consequently
suppresses
its
oncogenic
functions
vitro
vivo.
Moreover,
reveal
that
DUB3
bona
fide
deubiquitinase
YAP1,
which
functionally
links
CK2
stability
human
cancers.
Mechanistically,
CK2α
phosphorylates
at
Thr495,
thereby
facilitating
DUB3-mediated
deubiquitination
process
YAP1.
On
contrary,
loss
Thr495
phosphorylation
phosphorylation-defective
mutant
T495A,
cancer-related
D496H
failed
deubiquitinate
stabilize
effectively.
Notably,
upregulated
expressions
positively
correlate
with
overexpression.
Collectively,
our
findings
demonstrate
functional
significance
CK2α-DUB3
axis
stabilization
YAP1-driven
progression,
highlighting
strategies
might
be
benefit
management
lethal
aberrantly
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(3), С. 1229 - 1229
Опубликована: Янв. 30, 2025
The
burden
of
cancer
is
growing
in
almost
every
country.
Bone
metastases
significantly
affect
the
prognosis
and
lead
to
an
increase
mortality
morbidity.
management
cancer-induced
bone
pain
(CIBP)
still
shows
various
unmet
needs.
Opioid
use
burdened
by
a
number
possible
side
effects.
Moreover,
recent
progresses
treatment
increased
life
expectancy
patients,
even
those
with
metastatic
disease.
In
this
narrative
review,
we
reported
main
findings
regarding
TRP
channel
function
models.
cation
channels
play
key
role
different
functions
cells,
including
regulation
their
potential
for
metastasization,
are
involved
pathways
perception,
through
peripheral
central
Genetic
deletion
decreased
sensitivity
following
tumour
cell
inoculation.
Preclinical
data
suggest
modulators
some
channels,
such
as
TRPV1,
TRPA1,
TRPM7
TRPM8.
Clinical
results
scarce;
however,
physiological
modulating
remodelling
involvement
preclinical
models
have
garnered
interest
areas
research
last
few
years,
innovative
analgesic
strategies
that
may
overcome
long-term
effects
opioids.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 8, 2025
ABSTRACT
Approximately
50%
of
cancers
exhibit
decreased
CDKN2A
expression
(
Low
),
which
is
linked
to
immune
checkpoint
blockade
(ICB)
resistance.
While
traditionally
recognized
as
a
tumor
suppressor
and
cell
cycle
regulator,
we
have
previously
put
forth
new
paradigm
demonstrating
its
role
in
intracellular
metabolic
reprogramming.
Whether
the
derangement
due
loss
alters
metabolites
within
microenvironment
(TME)
how
that
affects
compartment
ICB
response
has
never
been
investigated.
Here
found
cancer
cells
reorganize
zinc
compartmentalization
by
upregulating
importer
SLC39A9
plasma
membrane,
leading
accumulation
concurrent
depletion
TME.
This
competition
for
results
zinc-starved
macrophages,
reduced
phagocytic
activity.
Remarkably,
restoring
levels
TME
through
dietary
intervention
re-educates
macrophages
pro-phagocytic
phenotype,
sensitizing
tumors
ICB.
Unexpectedly,
T
are
not
required
this
response.
Clinically,
from
patients
signatures,
corresponding
phagocytosis
signatures.
Moreover,
with
low
circulating
time-to-event
outcomes
compared
those
higher
levels.
Our
work
reveals
unrecognized
mechanism
outcompete
zinc,
directly
disrupting
their
function
efficacy.
