Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer
Molecular Cancer,
Год журнала:
2024,
Номер
23(1)
Опубликована: Ноя. 21, 2024
Metabolic
alterations,
a
hallmark
of
cancer,
enable
tumor
cells
to
adapt
their
environment
by
modulating
glucose,
lipid,
and
amino
acid
metabolism,
which
fuels
rapid
growth
contributes
treatment
resistance.
In
primary
breast
metabolic
shifts
such
as
the
Warburg
effect
enhanced
lipid
synthesis
are
closely
linked
chemotherapy
failure.
Similarly,
metastatic
lesions
often
display
distinct
profiles
that
not
only
sustain
but
also
confer
resistance
targeted
therapies
immunotherapies.
The
review
emphasizes
two
major
aspects:
mechanisms
driving
in
both
how
unique
environments
sites
further
complicate
treatment.
By
targeting
vulnerabilities
at
stages,
new
strategies
could
improve
efficacy
existing
provide
better
outcomes
for
cancer
patients.
Язык: Английский
Hsp90 Promotes Gastric Cancer Cell Metastasis and Stemness by Regulating the Regional Distribution of Glycolysis‐Related Metabolic Enzymes in the Cytoplasm
Advanced Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 14, 2024
Heat-shock
protein
90
(Hsp90)
plays
a
crucial
role
in
tumorigenesis
and
tumor
progression;
however,
its
mechanism
of
action
gastric
cancer
(GC)
remains
unclear.
Here,
the
Hsp90
GC
metabolism
is
focus
this
research.
High
expression
tissues
can
interact
with
glycolysis,
collectively
affecting
prognosis
clinical
samples.
Both
vitro
vivo
experiments
demonstrate
that
able
to
regulate
migration
stemness
properties
cells.
Metabolic
phenotype
analyses
indicate
influences
glycolytic
metabolism.
Mechanistically,
interacts
glycolysis-related
enzymes,
forming
multienzyme
complexes
enhance
glycolysis
efficiency
yield.
Additionally,
binds
cytoskeleton-related
proteins,
regulating
regional
distribution
enzymes
at
cell
margin
lamellar
pseudopods.
This
effect
could
lead
local
increase
efficient
energy
supply
from
further
promoting
epithelial-mesenchymal
transition
(EMT)
metastasis.
In
summary,
Hsp90,
through
interaction
metabolic
related
forms
multi-enzyme
regulates
by
dynamic
cytoskeletal
adjustments,
thereby
These
conclusions
also
support
potential
for
combined
targeted
approach
involving
cytoskeleton
therapy.
Язык: Английский
More than Just Protein Folding: The Epichaperome, Mastermind of the Cancer Cell
Cells,
Год журнала:
2025,
Номер
14(3), С. 204 - 204
Опубликована: Янв. 30, 2025
The
epichaperome,
a
dynamic
and
integrated
network
of
chaperone
proteins,
extends
its
roles
beyond
basic
protein
folding
to
stabilization
intracellular
signal
transduction
orchestrating
multitude
cellular
processes
critical
for
tumor
survival.
In
this
review,
we
explore
the
multifaceted
delving
into
diverse
locations,
factors
that
modulate
formation
function,
liquid–liquid
phase
separation,
key
signaling
crosstalk
pathways
it
regulates,
including
metabolism
transduction.
We
further
highlight
techniques
isolating
identifying
epichaperome
networks,
pitfalls,
opportunities.
Further,
review
profound
implications
cancer
treatment
therapy
design,
underscoring
need
strategic
engineering
hinges
on
comprehensive
insight
structure
workings
across
heterogeneous
cell
subpopulations
in
milieu.
By
presenting
holistic
view
epichaperome’s
functions
mechanisms,
aim
underscore
potential
as
target
novel
anti-cancer
strategies,
revealing
is
not
merely
piece
machinery
but
mastermind
facilitates
malignant
phenotype.
Язык: Английский
HSP90 co-regulates the formation and nuclear distribution of the glycolytic output complex to promote resistance and poor prognosis in gastric cancer patients
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Фев. 10, 2025
Resistance
to
treatment
is
a
critical
factor
contributing
poor
prognosis
in
gastric
cancer
patients.
HSP90
has
emerged
as
promising
therapeutic
target;
however,
its
role
regulating
tumor
metabolic
pathways,
particularly
glycolysis,
remains
poorly
understood,
which
limits
clinical
application.
We
identified
proteins
that
directly
interact
with
using
immunoprecipitation
(IP)
followed
by
mass
spectrometry.
The
relationship
between
and
glycolysis
was
further
investigated
through
transcriptomic
analyses
vitro
experiments.
Mechanistic
insights
were
obtained
spectrometry,
co-immunoprecipitation
(Co-IP)
assays,
drug
sensitivity
tests,
bioinformatics
analyses.
Additionally,
we
developed
scoring
system
based
on
data
evaluate
prognostic
significance
association
resistance
Our
multi-omics
studies
revealed
regulates
influences
the
stemness
properties
of
cells.
Mechanistically,
facilitates
assembly
glycolytic
multi-enzyme
complex,
termed
HGEO
enhances
metabolism.
formation
multienzyme
complex
comprising
key
enzymes
including
PGK1,
PKM2,
ENO1,
LDHA,
thereby
facilitating
production
final
products.
refer
this
"HSP90-Glycolytic
Output
Complex"
(HGEO
Complex).
quantified
phenomenon
(HGScore),
finding
patients
high
HGScore
exhibited
more
malignant
signatures,
increased
treatment,
poorer
prognoses.
Furthermore,
demonstrated
localized
nucleus,
regulated
nuclear
lamina
protein
LMNA,
contributes
adverse
outcomes.
In
experiments
indicated
inhibiting
sensitizes
cells
chemotherapy.
findings
suggest
LMNA
mediated
localization
enhancing
traits
mechanisms
cancer.
Targeting
pathway
may
offer
novel
strategy
improve
Язык: Английский