Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Ноя. 18, 2024
Abstract
The
oncogene
xCT
plays
an
indispensable
role
in
tumor
growth
by
protecting
cancer
cells
from
oxidative
stress
and
ferroptosis.
Emerging
evidence
indicated
function
is
tightly
controlled
posttranslational
modifications,
especially
ubiquitination.
However,
it
still
remains
unclear
what
specific
regulatory
mechanism
of
ubiquitin
ligases
human
cancers.
Here,
we
reported
that
NEDD4L,
E3
ligases,
inhibited
esophageal
squamous
cell
carcinoma
(ESCC)
facilitated
ferroptosis
ubiquitination
xCT.
NEDD4L
expression
was
declined
ESCC
associated
with
invasion,
lymph
node
metastasis
distant
metastasis.
Silencing
triggered
growth.
Meanwhile,
knock
down
prevented
the
accumulation
ROS,
elevated
level
GSH,
reduced
content
MDA
cells,
thereby
inhibiting
Mechanistically,
directly
bound
to
∆CT
domain
through
its
WW
HECT
domain.
More
importantly,
promoted
degradation
facilitating
polyubiquitination
cells.
Collectively,
these
findings
suggest
crucial
governing
stability
mediating
ESCC.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Март 8, 2024
Ferroptosis
is
a
non-apoptotic
form
of
regulated
cell
death
characterized
by
the
lethal
accumulation
iron-dependent
membrane-localized
lipid
peroxides.
It
acts
as
an
innate
tumor
suppressor
mechanism
and
participates
in
biological
processes
tumors.
Intriguingly,
mesenchymal
dedifferentiated
cancer
cells,
which
are
usually
resistant
to
apoptosis
traditional
therapies,
exquisitely
vulnerable
ferroptosis,
further
underscoring
its
potential
treatment
approach
for
cancers,
especially
refractory
cancers.
However,
impact
ferroptosis
on
extends
beyond
direct
cytotoxic
effect
cells.
induction
not
only
inhibits
but
also
promotes
development
due
negative
anticancer
immunity.
Thus,
comprehensive
understanding
role
crucial
successful
translation
therapy
from
laboratory
clinical
applications.
In
this
review,
we
provide
overview
recent
advancements
cancer,
covering
molecular
mechanisms,
functions,
regulatory
pathways,
interactions
with
microenvironment.
We
summarize
applications
immunotherapy,
radiotherapy,
systemic
therapy,
well
inhibition
various
conditions.
finally
discuss
markers,
current
challenges
future
directions
cancer.
Molecular Biomedicine,
Год журнала:
2023,
Номер
4(1)
Опубликована: Окт. 16, 2023
Abstract
Ferroptosis,
a
regulated
form
of
cellular
death
characterized
by
the
iron-mediated
accumulation
lipid
peroxides,
provides
novel
avenue
for
delving
into
intersection
metabolism,
oxidative
stress,
and
disease
pathology.
We
have
witnessed
mounting
fascination
with
ferroptosis,
attributed
to
its
pivotal
roles
across
diverse
physiological
pathological
conditions
including
developmental
processes,
metabolic
dynamics,
oncogenic
pathways,
neurodegenerative
cascades,
traumatic
tissue
injuries.
By
unraveling
intricate
underpinnings
molecular
machinery,
contributors,
signaling
conduits,
regulatory
networks
governing
researchers
aim
bridge
gap
between
intricacies
this
unique
mode
multifaceted
implications
health
disease.
In
light
rapidly
advancing
landscape
ferroptosis
research,
we
present
comprehensive
review
aiming
at
extensive
in
origins
progress
human
diseases.
This
concludes
careful
analysis
potential
treatment
approaches
carefully
designed
either
inhibit
or
promote
ferroptosis.
Additionally,
succinctly
summarized
therapeutic
targets
compounds
that
hold
promise
targeting
within
various
facet
underscores
burgeoning
possibilities
manipulating
as
strategy.
summary,
enriched
insights
both
investigators
practitioners,
while
fostering
an
elevated
comprehension
latent
translational
utilities.
revealing
basic
processes
investigating
possibilities,
crucial
resource
scientists
medical
aiding
deep
understanding
effects
situations.
Redox Biology,
Год журнала:
2023,
Номер
62, С. 102677 - 102677
Опубликована: Март 17, 2023
Ferroptosis,
an
iron-dependent
lipid
peroxidation-driven
programmed
cell
death,
is
closely
related
to
cancer
therapy.
The
development
of
druggable
ferroptosis
inducers
and
their
rational
application
in
therapy
are
critical.
Here,
we
identified
Tubastatin
A,
HDAC6
inhibitor
as
a
novel
inducer
through
large-scale
drug
screening.
A
directly
bonded
GPX4
inhibited
enzymatic
activity
biotin-linked
putdown
LC/MS
analysis,
which
independent
its
inhibition
HDAC6.
In
addition,
our
results
showed
that
radiotherapy
not
only
activated
Nrf2-mediated
transcription
but
also
lysosome-mediated
degradation,
subsequently
inducing
tolerance
radioresistance
cells.
overcame
resistance
cells
by
inhibiting
activity.
More
importantly,
has
excellent
bioavailability,
demonstrated
ability
significantly
promote
radiotherapy-induced
peroxidation
tumour
suppression
mouse
xenograft
model.
Our
findings
identify
inducer,
enhances
radiotherapy-mediated
antitumor
effects.
This
work
provides
compelling
rationale
for
the
clinical
evaluation
especially
combination
with
radiotherapy.
International Journal of Biological Sciences,
Год журнала:
2023,
Номер
19(11), С. 3558 - 3575
Опубликована: Янв. 1, 2023
Ferroptosis
is
a
form
of
programmed
cell
death
characterized
by
elevated
intracellular
ferrous
ion
levels
and
increased
lipid
peroxidation.Since
its
discovery
characterization
in
2012,
considerable
progress
has
been
made
understanding
the
regulatory
mechanisms
pathophysiological
functions
ferroptosis.Recent
findings
suggest
that
numerous
organ
injuries
(e.g.,
ischemia/reperfusion
injury)
degenerative
pathologies
aortic
dissection
neurodegenerative
disease)
are
driven
ferroptosis.Conversely,
insufficient
ferroptosis
linked
to
tumorigenesis.Furthermore,
recent
study
revealed
effect
on
hematopoietic
stem
cells
under
physiological
conditions.The
identified
date
include
mainly
iron
metabolism,
such
as
transport
ferritinophagy,
redox
systems,
glutathione
peroxidase
4
(GPX4)-glutathione
(GSH),
ferroptosis-suppressor-protein
1
(FSP1)-CoQ10,
FSP1-vitamin
K
(VK),
dihydroorotate
dehydrogenase
(DHODH)-CoQ,
GTP
cyclohydrolase
(GCH1)-tetrahydrobiopterin
(BH4).Recently,
an
increasing
number
studies
have
demonstrated
important
role
played
epigenetic
mechanisms,
especially
DNA,
RNA,
protein
methylation,
ferroptosis.In
this
review,
we
provide
critical
analysis
molecular
networks
date,
with
focus
methylation.Furthermore,
discuss
some
debated
unanswered
questions
should
be
foci
future
research
field.
Experimental Hematology and Oncology,
Год журнала:
2024,
Номер
13(1)
Опубликована: Май 22, 2024
Abstract
Radiotherapy
is
one
of
the
mainstream
approaches
for
cancer
treatment,
although
clinical
outcomes
are
limited
due
to
radioresistance
tumor
cells.
Hypoxia
and
metabolic
reprogramming
hallmarks
initiation
progression
closely
linked
radioresistance.
Inside
a
tumor,
rate
angiogenesis
lags
behind
cell
proliferation,
underdevelopment
abnormal
functions
blood
vessels
in
some
loci
result
oxygen
deficiency
cells,
i.e.,
hypoxia.
This
prevents
radiation
from
effectively
eliminating
hypoxic
Cancer
cells
switch
glycolysis
as
main
source
energy,
phenomenon
known
Warburg
effect,
sustain
their
rapid
proliferation
rates.
Therefore,
pathways
involved
hypoxia-induced
promising
intervention
targets
treatment.
In
this
review,
we
discussed
mechanisms
underlying
hypoxia
detail,
including
DNA
repair,
role
stem
oxidative
stress
relief,
autophagy
regulation,
immune
escape.
addition,
proposed
existence
feedback
loop
between
energy
hypoxia,
which
associated
with
development
exacerbation
tumors.
Simultaneous
blockade
other
tumor-specific
can
be
an
effective
approach
overcome
comprehensive
overview
provides
new
insights
into
radiosensitivity
progression.
Advanced Materials,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 5, 2024
Radiotherapy
(RT),
essential
for
treating
various
cancers,
faces
challenges
from
tumor
hypoxia,
which
induces
radioresistance.
A
tumor-targeted
"prosthetic-Arginine"
coassembled
nanozyme
system,
engineered
to
catalytically
generate
nitric
oxide
(NO)
and
oxygen
(O
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 and Disease,
Год журнала:
2025,
Номер
16(1)
Опубликована: Апрель 5, 2025
Abstract
Radiotherapy,
as
a
vital
means
of
esophageal
cancer
treatment,
has
benefited
countless
patients,
but
owing
to
the
occurrence
radio-resistance,
its
therapeutic
efficiency
been
dramatically
mitigated.
Discovering
key
biomarkers
governing
radio-tolerance
in
and
revealing
their
inherent
molecular
mechanisms
will
be
great
significance
for
clinical
treatment.
Here,
we
have
found
roundabout
guidance
receptor
1
(ROBO1)
was
significantly
upregulated
cancerous
tissues
showed
enhanced
expression
with
development
staging.
Cellular
experiments
demonstrated
ROBO1
directly
interacted
eukaryotic
translation
initiation
factor
3A
(eIF3A)
accelerated
degradation
cells
after
irradiation
Mass
spectrum
analysis
further
revealed
that
response
irradiation,
ROBO1,
eIF3A
G3BP2
(Ras
GTPase-activating
protein-binding
protein
2)
formed
hetero-complex
triggered
lysosomes-mediated
degradation.
Knocking
down
abrogated
influence
on
instability.
Besides,
ROBO1-mediated
interrupted
P53
process
which
turn
provoked
downstream
mTOR
signaling
increased
DNA
repair
associated
genes
expressions,
resulting
radio-resistance
enhancement
cells.
In
conclusion,
our
findings
novel
role
modulating
P53/mTOR
activity
provided
drug
candidate
overcoming
cancer.
Advanced Materials,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 9, 2024
Abstract
During
fractionated
radiotherapy,
DNA
damage
repair
intensifies
in
tumor
cells,
culminating
cancer
radioresistance
and
subsequent
radiotherapy
failure.
Despite
the
recent
development
of
nanoradiosensitizers
targeting
specific
pathways,
persistence
mechanisms
involving
multiple
pathways
remains
inevitable.
To
address
this
challenge,
a
nucleophilicity‐engineered
ligation
blockade
nanoradiosensitizer
(DLBN)
comprising
Au/CeO
2
heteronanostructure
modified
with
trans‐acting
activator
transcription
peptides
is
reported,
which
targets
inhibits
inside
cell
nuclei
via
heterointerface‐mediated
dephosphorylation
DNA,
crucial
step
overcoming
radioresistance.
First,
Schottky‐type
nucleus‐targeting
DLBN
effectively
radiation‐induced
catalase‐mimetic
activity
radiation‐triggered
catalytic
reactions.
Notably,
by
leveraging
heterointerface,
spontaneously
dissociates
H
O
to
hydroxide,
nucleophile
higher
nucleophilicity,
thereby
exhibiting
remarkable
capability
at
nicks
through
facilitated
nucleophilic
attack.
This
enables
ligation,
pivotal
all
interrupting
process.
Consequently,
resensitizes
radioresistant
cells
therapy‐induced
radioresistance,
leading
substantial
accumulation
unrepaired
damage.
These
findings
offer
insight
into
within
nuclei,
underscore
potential
heteronanostructure‐based
block
against
