Abstract
Cuproptosis,
the
current
form
of
regulated
cell
death
characterized
by
copper
overload,
oligomerization
lipoacylated
proteins,
and
loss
Fe–S
cluster
has
been
proposed
to
function
closely
with
human
diseases,
including
cancer.
Since
its
first
identification
in
2022,
many
strategies
have
developed
induce
cuproptosis
for
cancer
therapy,
such
as
small‐molecule
drugs
nanomaterials.
Although
reviews
related
reported,
they
remain
at
a
basic
mechanism
level,
summary
covering
recent
progress
field
nanotechnologies
cuproptosis‐based
therapy
not
yet
presented.
Therefore,
it
is
time
fill
gap
shed
light
on
future
directions
application
this
promising
tool
fight
against
In
minireview,
we
expounded
action
emphasized
feasibility
triggering
therapy.
The
treatments
based
nanoparticle‐induced
was
then
described.
Finally,
challenges
development
emerging
are
also
discussed.
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Окт. 2, 2022
Liver
metastasis
is
highly
aggressive
and
treatment-refractory,
partly
due
to
macrophage-mediated
immune
suppression.
Understanding
the
mechanisms
leading
functional
reprogramming
of
macrophages
in
tumor
microenvironment
(TME)
will
benefit
cancer
immunotherapy.
Herein,
we
find
that
scavenger
receptor
CD36
upregulated
metastasis-associated
(MAMs)
deletion
MAMs
attenuates
liver
mice.
contain
more
lipid
droplets
have
unique
capability
engulfing
cell-derived
long-chain
fatty
acids,
which
are
carried
by
extracellular
vesicles.
The
lipid-enriched
vesicles
preferentially
partitioned
into
via
CD36,
fuel
trigger
their
tumor-promoting
activities.
In
patients
with
metastases,
high
expression
correlates
protumoral
M2-type
infiltration,
creating
a
immunosuppressive
TME.
Collectively,
our
findings
uncover
mechanism
cells
metabolically
interact
TME,
suggest
therapeutic
potential
targeting
as
immunotherapy
for
metastasis.
Journal of Hematology & Oncology,
Год журнала:
2023,
Номер
16(1)
Опубликована: Сен. 12, 2023
Abstract
Lipid
metabolic
reprogramming
is
an
emerging
hallmark
of
cancer.
In
order
to
sustain
uncontrolled
proliferation
and
survive
in
unfavorable
environments
that
lack
oxygen
nutrients,
tumor
cells
undergo
transformations
exploit
various
ways
acquiring
lipid
increasing
oxidation.
addition,
stromal
immune
the
microenvironment
also
reprogramming,
which
further
affects
functional
phenotypes
responses.
Given
metabolism
plays
a
critical
role
supporting
cancer
progression
remodeling
microenvironment,
targeting
pathway
could
provide
novel
approach
treatment.
This
review
seeks
to:
(1)
clarify
overall
landscape
mechanisms
cancer,
(2)
summarize
landscapes
within
their
roles
progression,
(3)
potential
therapeutic
targets
for
metabolism,
highlight
combining
such
approaches
with
other
anti-tumor
therapies
new
opportunities
patients.
Changes
in
mitochondrial
morphology
are
associated
with
nutrient
utilization,
but
the
precise
causalities
and
underlying
mechanisms
remain
unknown.
Here,
using
cellular
models
representing
a
wide
variety
of
shapes,
we
show
strong
linear
correlation
between
fragmentation
increased
fatty
acid
oxidation
(FAO)
rates.
Forced
elongation
following
MFN2
over-expression
or
DRP1
depletion
diminishes
FAO,
while
forced
upon
knockdown
knockout
augments
FAO
as
evident
from
respirometry
metabolic
tracing.
Remarkably,
genetic
induction
phenocopies
distinct
cell
type-specific
biological
functions
enhanced
FAO.
These
include
stimulation
gluconeogenesis
hepatocytes,
insulin
secretion
islet
β-cells
exposed
to
acids,
survival
FAO-dependent
lymphoma
subtypes.
We
find
that
increases
long-chain
not
short-chain
identifying
carnitine
O-palmitoyltransferase
1
(CPT1)
downstream
effector
regulation
Mechanistically,
determined
reduces
malonyl-CoA
inhibition
CPT1,
CPT1
sensitivity
inhibition.
Overall,
these
findings
underscore
physiologic
role
for
mechanism
whereby
fuel
preference
capacity
determined.
