Abstract
Tumor
tissues
exhibit
elevated
oxidative
stress,
with
the
cystine‐glutamate
transporter
x
CT
solute
carrier
family
7
member
11
(
CT/SLC7A11)
protecting
cancer
cells
from
damage
by
facilitating
cystine
uptake
for
glutathione
synthesis.
Disulfidptosis,
a
newly
identified
form
of
programmed
cell
death
(PCD),
occurs
in
high
CT/SLC7A11
expression
under
glucose‐deprived
conditions.
Distinct
other
PCD
pathways,
disulfidptosis
is
characterized
aberrant
disulfide
bond
formation
and
cellular
dysfunction,
ultimately
resulting
death.
This
novel
mechanism
offers
remarkable
therapeutic
potential
targeting
inherent
stress
vulnerabilities
rapidly
growing
cells.
Advances
nanotechnology
enable
development
nanomaterials
capable
inducing
reactive
oxygen
species
(ROS)
generation,
disrupting
bonds.
In
addition,
they
are
to
deliver
agents
directly
tumors,
thereby
improving
precision
minimizing
off‐target
effects.
Moreover,
combining
ROS‐induced
immunogenic
can
remodel
tumor
microenvironment
enhance
anti‐tumor
immunity.
review
explores
mechanisms
underlying
disulfidptosis,
its
treatment,
synergistic
role
amplifying
Selective
induction
using
represents
promising
strategy
achieving
more
effective,
selective,
less
toxic
therapies.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июль 8, 2024
The
non-natriuretic-dependent
glutamate/cystine
inverse
transporter-system
Xc-
is
composed
of
two
protein
subunits,
SLC7A11
and
SLC3A2,
with
serving
as
the
primary
functional
component
responsible
for
cystine
uptake
glutathione
biosynthesis.
implicated
in
tumor
development
through
its
regulation
redox
homeostasis,
amino
acid
metabolism,
modulation
immune
function,
induction
programmed
cell
death,
among
other
processes
relevant
to
tumorigenesis.
In
this
paper,
we
summarize
structure
biological
functions
SLC7A11,
discuss
potential
role
therapy,
which
provides
a
new
direction
precision
personalized
treatment
tumors.
Clinical and Experimental Medicine,
Год журнала:
2025,
Номер
25(1)
Опубликована: Янв. 3, 2025
Donafenib
is
an
improved
version
of
sorafenib
in
which
deuterium
substituted
into
the
drug's
chemical
structure,
enhancing
its
stability
and
antitumor
activity.
exhibits
enhanced
activity
better
tolerance
than
preclinical
clinical
studies.
However,
specific
mechanism
effect
on
hepatocellular
carcinoma
has
not
been
reported.
Iron
deposition
a
cell
death
pattern
caused
by
disturbances
iron
metabolism.
Apoptosis
form
programmed
death.
They
may
interact
with
each
other
during
This
study
mainly
explores
potential
donafenib
activating
p53
signaling
pathway,
inducing
deposition,
apoptosis
carcinoma.
Hepa1-6
Huh7
cells
were
treated
various
concentrations
donafenib.
Scratch
healing
pore
migration
tests
conducted.
Analyze
through
flow
cytometry
TUNEL
fluorescence
labeling.
RNA
sequencing
was
conducted
both
untreated
donafenib-treated
cells.
The
key
proteins
involved
ferroptosis
(SLC7A11,
GPX4)
(caspase3,
caspase8,
Bax,
Bcl-2,
p53)
then
evaluated
using
immunoblotting
immunohistochemical
staining.
Reactive
oxygen
species
(ROS)
levels
cancer
measured.
treatment
resulted
dose-dependent
decrease
proliferation,
migration,
invasion
capabilities
There
increase
rates
ROS
accumulation,
reduction
tumor
volume.
underwent
significant
changes.
activates
induce
ferroptosis,
enhance
apoptosis,
suggesting
as
effective
therapeutic
agent
for
HCC.
Clinical and Translational Medicine,
Год журнала:
2025,
Номер
15(3)
Опубликована: Фев. 25, 2025
Glioblastoma
multiforme
(GBM)is
a
highly
aggressive
malignancy
of
the
central
nervous
system
characterized
by
poor
survival
rates.
Ferroptosis,
an
iron-dependent
cell
death
pathway,
is
promising
therapeutic
target
for
GBM.
However,
current
treatments
targeting
pathways
have
not
yielded
expected
results.
Long
noncoding
RNAs
(lncRNAs)
been
implicated
in
tumour
proliferation,
however,
their
role
ferroptosis
GBM
remains
underexplored.
This
study
investigated
interplay
between
lncRNA
LINC01088
and
to
identify
novel
strategies.
We
conducted
gain-
loss-of-function
studies
assess
impact
on
tumourigenesis
both
vitro
vivo.
Bioinformatics,
dual-luciferase
reporter
assays,
chromatin
immunoprecipitation,
RNA
pulldown,
mass
spectrometry,
immunoprecipitation
(RIP),
transcriptome
sequencing
were
utilized
elucidate
mechanisms
underlying
expression
its
downstream
effects
ferroptosis.
The
transcription
factor
specificity
protein
1
(SP1)
was
identified
as
promoter
transcription,
which
facilitated
progression.
found
inhibit
promote
malignancy.
Mechanistically,
stabilized
HLTF
enhancing
interaction
with
USP7
preventing
ubiquitin-mediated
degradation.
stabilization
led
upregulation
SLC7A11,
inhibits
Rescue
experiments
confirmed
that
altering
levels
reversed
ferroptotic
phenotypes
associated
modulation.
revealed
SP1/LINC01088/HLTF/USP7/SLC7A11
axis
regulates
GBM,
highlighting
potential
ferroptosis-dependent
treatment.
transcriptionally
upregulated
SP1.
acts
scaffold
platform
bind
HLTF.
USP7,
deubiquitinating
enzyme
HLTF,
participates
inhibiting
ubiquitin-proteasome
degradation
upregates
cells
inhibited.
Journal of Cellular and Molecular Medicine,
Год журнала:
2024,
Номер
28(13)
Опубликована: Июль 1, 2024
Hepatocellular
carcinoma
(HCC),
a
prevalent
malignancy
worldwide,
poses
significant
challenges
in
terms
of
prognosis,
necessitating
innovative
therapeutic
approaches.
Ferroptosis
offers
notable
advantages
over
apoptosis,
holding
promise
as
novel
approach
for
HCC
complexities.
Moreover,
while
the
interaction
between
long
non-coding
RNAs
(lncRNAs)
and
mRNAs
is
pivotal
various
physiological
pathological
processes,
their
involvement
ferroptosis
remains
relatively
unexplored.
In
this
study,
we
constructed
ferroptosis-related
lncRNA-mRNA
correlation
network
using
Pearson
analysis.
Notably,
SLC7A11-AS1/SLC7A11
pair,
exhibiting
high
correlation,
was
identified.
Bioinformatics
analysis
revealed
expression
levels
pair
key
clinical
characteristics
patients,
including
gender,
pathology,
Ishak
scores
tumour
size.
And
poor
prognosis
associated
with
pair.
Functional
experiments
demonstrated
that
SLC7A11-AS1,
by
binding
to
3'UTR
region
SLC7A11
mRNA,
enhanced
its
stability,
thereby
promoting
cell
growth
resistance
erastin-
induced
ferroptosis.
Additionally,
vivo
studies
confirmed
SLC7A11-AS1
knockdown
potentiated
inhibitory
effects
erastin
on
growth.
Overall,
our
findings
suggest
targeting
holds
potential
strategy
patients.
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Окт. 11, 2024
Disulfidptosis
is
a
novel
discovered
form
of
programmed
cell
death
(PCD)
that
diverges
from
apoptosis,
necroptosis,
ferroptosis,
and
cuproptosis,
stemming
disulfide
stress-induced
cytoskeletal
collapse.
In
cancer
cells
exhibiting
heightened
expression
the
solute
carrier
family
7
member
11
(SLC7A11),
excessive
cystine
importation
reduction
will
deplete
nicotinamide
adenine
dinucleotide
phosphate
(NADPH)
under
glucose
deprivation,
followed
by
an
increase
in
intracellular
stress
aberrant
bond
formation
within
actin
networks,
ultimately
culminating
collapse
disulfidptosis.
involves
crucial
physiological
processes
eukaryotic
cells,
such
as
uptake,
NADPH
metabolism,
dynamics.
The
Rac1-WRC
pathway-mediated
polymerization
also
implicated
this
due
to
its
contribution
formation.
However,
precise
mechanisms
underlying
disulfidptosis
role
tumors
are
not
well
understood.
This
probably
multifaceted
functionalities
SLC7A11
complexities
downstream
pathways
driving
review
describes
critical
roles
summarizes
recent
research
advancements
potential
Moreover,
less-studied
aspects
newly
process
highlighted
stimulate
further
investigations
field.
Frontiers in Genetics,
Год журнала:
2024,
Номер
15
Опубликована: Апрель 17, 2024
Ovarian
cancer
(OC)
is
the
deadliest
malignancy
in
gynecology,
but
mechanism
of
its
initiation
and
progression
poorly
elucidated.
Disulfidptosis
a
novel
discovered
type
regulatory
cell
death.
This
study
aimed
to
develop
disulfidptosis-related
prognostic
signature
(DRPS)
for
OC
explore
effects
potential
treatment
by
risk
stratification.
Biomolecules,
Год журнала:
2024,
Номер
14(8), С. 908 - 908
Опубликована: Июль 25, 2024
Post-translational
modifications
(PTMs)
influence
protein
functionality
by
modulating
stability,
localization,
and
interactions
with
other
molecules,
thereby
controlling
various
cellular
processes.
Common
PTMs
include
phosphorylation,
acetylation,
ubiquitination,
glycosylation,
SUMOylation,
methylation,
sulfation,
nitrosylation.
Among
these
modifications,
O-GlcNAcylation
has
been
shown
to
play
a
critical
role
in
cancer
development
progression,
especially
hepatocellular
carcinoma
(HCC).
This
review
outlines
the
of
progression
HCC.
Moreover,
we
delve
into
underlying
mechanisms
HCC
highlight
compounds
that
target
O-GlcNAc
transferase
(OGT)
O-GlcNAcase
(OGA)
improve
treatment
outcomes.
Understanding
will
offer
insights
potential
therapeutic
strategies
targeting
OGT
OGA,
which
could
for
patients
Chinese Medical Journal,
Год журнала:
2024,
Номер
137(7), С. 818 - 829
Опубликована: Март 18, 2024
Abstract
Lung
cancer
is
one
of
the
most
common
malignancies
and
has
highest
number
deaths
among
all
cancers.
Despite
continuous
advances
in
medical
strategies,
overall
survival
lung
patients
still
low,
probably
due
to
disease
progression
or
drug
resistance.
Ferroptosis
an
iron-dependent
form
regulated
cell
death
triggered
by
lethal
accumulation
lipid
peroxides,
its
dysregulation
implicated
development.
Preclinical
evidence
shown
that
targeting
ferroptosis
pathway
could
be
a
potential
strategy
for
improving
treatment
outcomes.
In
this
review,
we
summarize
underlying
mechanisms
regulatory
networks
highlight
ferroptosis-targeting
preclinical
attempts
provide
new
insights
treatment.
