Metabolic adaptations in prostate cancer
British Journal of Cancer,
Journal Year:
2024,
Volume and Issue:
131(8), P. 1250 - 1262
Published: July 5, 2024
Prostate
cancer
is
one
of
the
most
commonly
diagnosed
cancers
in
men
and
a
major
cause
cancer-related
deaths
worldwide.
Among
molecular
processes
that
contribute
to
this
disease,
weight
metabolism
has
been
placed
under
limelight
recent
years.
Tumours
exhibit
metabolic
adaptations
comply
with
their
biosynthetic
needs.
However,
metabolites
also
play
an
important
role
supporting
cell
survival
challenging
environments
or
remodelling
tumour
microenvironment,
thus
being
recognized
as
hallmark
cancer.
uniquely
driven
by
androgen
receptor
signalling,
knowledge
influenced
paths
research.
This
review
provides
comprehensive
perspective
on
support
prostate
progression
beyond
particular
focus
intrinsic
extrinsic
pathways.
Language: Английский
Enzalutamide Sensitizes Castration‐Resistant Prostate Cancer to Copper‐Mediated Cell Death
Xiang Gao,
No information about this author
Haolin Zhao,
No information about this author
Jiao Liu
No information about this author
et al.
Advanced Science,
Journal Year:
2024,
Volume and Issue:
11(30)
Published: June 10, 2024
Despite
the
initial
efficacy
of
enzalutamide
in
castration-resistant
prostate
cancer
(CRPC),
inevitable
resistance
remains
a
significant
challenge.
Here,
synergistic
induction
copper-dependent
cell
death
(cuproptosis)
CRPC
cells
is
reported
by
and
copper
ionophores
(elesclomol/disulfiram).
Mechanistically,
treatment
increases
mitochondrial
dependence
cells,
rendering
them
susceptible
to
cuproptosis,
as
evidenced
specific
reversal
with
chelator
tetrathiomolybdate.
This
susceptibility
characterized
hallmarks
including
lipoylated
protein
aggregation
iron-sulfur
cluster
instability.
Interestingly,
matrix
reductase,
FDX1,
specifically
correlates
elesclomol
sensitivity,
suggesting
potential
mechanistic
divergence
between
two
ionophores.
Notably,
this
effect
extends
beyond
vitro
models,
demonstrating
22Rv1
xenografts,
mouse
Pten
p53
knockout
organoids.
Importantly,
significantly
enhances
ionophore-mediated
cytotoxicity
enzalutamide-resistant
cells.
Collectively,
these
findings
indicate
that
synergistically
induce
offering
promising
therapeutic
avenue
for
CRPC,
potentially
cases.
Language: Английский
MED12 and CDK8/19 modulate androgen receptor activity and enzalutamide response in prostate cancer
Chiara Andolfi,
No information about this author
Caterina Bartolini,
No information about this author
Elisa Morales
No information about this author
et al.
Endocrinology,
Journal Year:
2024,
Volume and Issue:
165(10)
Published: Aug. 27, 2024
Abstract
Prostate
cancer
progression
is
driven
by
androgen
receptor
(AR)
activity,
which
a
target
for
therapeutic
approaches.
Enzalutamide
an
AR
inhibitor
that
prolongs
the
survival
of
patients
with
advanced
prostate
cancer.
However,
resistance
mechanisms
arise
and
impair
its
efficacy.
One
these
expression
AR-V7,
constitutively
active
splice
variant.
The
Mediator
complex
multisubunit
protein
modulates
gene
on
genome-wide
scale.
MED12
cyclin-dependent
kinase
(CDK)8,
or
paralog
CDK19,
are
components
module
regulates
proliferation
cells.
In
this
study,
we
investigated
how
CDK8/19
influence
cancer-driven
processes
in
cell
lines,
focusing
activity
enzalutamide
response.
We
inhibited
LNCaP
(AR+,
enzalutamide-sensitive),
22Rv1
(AR-V7+,
enzalutamide-resistant),
PC3
(AR−,
enzalutamide-insensitive)
Both
inhibition
reduced
all
respective
3D
spheroids.
knockdown
significantly
c-Myc
signaling
pathways.
cells,
it
consistently
response,
prostate-specific
antigen
(PSA)
secretion,
genes,
AR-V7
expression.
Combined
enzalutamide,
additively
decreased
both
PSA
secretion
cells
and,
when
combined
Our
study
revealed
regulate
their
may
modulate
response
to
Language: Английский
Mitochondrial Elongation and ROS-Mediated Apoptosis in Prostate Cancer Cells under Therapy with Apalutamide and Complex I Inhibitor
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(13), P. 6939 - 6939
Published: June 25, 2024
Metabolic
reprogramming
and
mitochondrial
dynamics
are
pivotal
in
prostate
cancer
(PCa)
progression
treatment
resistance,
making
them
essential
targets
for
therapeutic
intervention.
In
this
study,
we
investigated
the
effects
of
androgen
receptor
antagonist
apalutamide
(ARN)
electron
transport
chain
complex
I
inhibitor
IACS-010759
(IACS)
on
network
architecture
PCa
cells.
Treatment
with
ARN
and/or
IACS
induced
significant
changes
morphology,
particularly
elongation,
androgen-sensitive
Additionally,
modulated
fission
fusion
processes,
indicating
a
convergence
metabolic
androgen-signaling
pathways
shaping
function.
Notably,
combination
resulted
increased
apoptotic
cell
death
oxidative
stress
selectively
Our
findings
highlight
potential
targeting
metabolism
emphasize
need
further
mechanistic
understanding
to
optimize
strategies
improve
patient
outcomes.
Language: Английский
PGC-1α drives small cell neuroendocrine cancer progression towards an ASCL1-expressing subtype with increased mitochondrial capacity
Grigor Varuzhanyan,
No information about this author
Chia‐Chun Chen,
No information about this author
Jack Freeland
No information about this author
et al.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: April 13, 2024
ABSTRACT
Adenocarcinomas
from
multiple
tissues
can
evolve
into
lethal,
treatment-resistant
small
cell
neuroendocrine
(SCN)
cancers
comprising
subtypes
with
poorly
defined
metabolic
characteristics.
The
role
of
metabolism
in
directly
driving
subtype
determination
remains
unclear.
Through
bioinformatics
analyses
thousands
patient
tumors,
we
identified
enhanced
PGC-1α—a
potent
regulator
oxidative
phosphorylation
(OXPHOS)—in
various
SCN
(SCNCs),
closely
linked
differentiation.
In
a
patient-derived
prostate
tissue
SCNC
transformation
system,
the
ASCL1-expressing
showed
elevated
PGC-1α
expression
and
increased
OXPHOS
activity.
Inhibition
reduced
proliferation
lung
cancer
lines
blocked
tumor
formation.
Conversely,
enhancing
PGC-
1α
OXPHOS,
validated
by
small-animal
Positron
Emission
Tomography
mitochondrial
imaging,
tripled
formation
rate
promoted
commitment
to
ASCL1
lineage.
These
results
establish
as
driver
progression
determination,
highlighting
novel
vulnerabilities
SCNCs
across
different
tissues.
STATEMENT
OF
SIGNIFICANCE
Our
study
provides
functional
evidence
that
reprogramming
impact
phenotypes
establishes
PGC-1α-induced
lineage
determination.
mechanistic
insights
reveal
common
originating
tissues,
opening
new
avenues
for
pan-SCN
therapeutic
strategies.
Language: Английский
A Metabolic–Epigenetic Mechanism Directs Cell Fate and Therapeutic Sensitivity in Breast Cancer
Cancer Research,
Journal Year:
2024,
Volume and Issue:
84(9), P. 1382 - 1383
Published: Feb. 8, 2024
Abstract
Over
the
past
decade,
studies
have
increasingly
shed
light
on
a
reciprocal
relationship
between
cellular
metabolism
and
cell
fate,
meaning
that
cell's
lineage
both
drives
is
governed
by
its
specific
metabolic
features.
A
recent
study
Zhang
colleagues,
published
in
Cell
Metabolism,
describes
novel
metabolic–epigenetic
regulatory
axis
governs
identity
triple-negative
breast
cancer
(TNBC).
Among
key
findings,
authors
demonstrate
enzyme
pyruvate
kinase
M2
(PKM2)
directly
binds
to
histone
methyltransferase
enhancer
of
zeste
homolog
2
(EZH2)
nucleus
silence
expression
set
genes
includes
mitochondrial
carnitine
transporter
SLC16A9.
Perturbation
this
mechanism
induces
shift
away
from
glycolysis
toward
fatty
acid
oxidation.
The
ensuing
influx
facilitates
deposition
activating
epigenetic
mark
H3K27Ac
onto
promoter
GATA3,
driving
committed
luminal
state.
Importantly,
represents
potentially
targetable
vulnerability
for
treatment
TNBC,
subtype
currently
lacks
effective
therapeutic
strategies.
These
findings
lend
further
support
paradigm
underlying
our
understanding
metabolism:
fuel
source
functions
not
only
provide
energy
but
also
direct
regulation
fate.
Language: Английский
UBXN1 promotes liver tumorigenesis by regulating mitochondrial homeostasis
Kun Jiao,
No information about this author
Guiqin Xu,
No information about this author
Yun Liu
No information about this author
et al.
Journal of Translational Medicine,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: May 21, 2024
The
maintenance
of
mitochondrial
homeostasis
is
critical
for
tumor
initiation
and
malignant
progression
because
it
increases
cell
survival
growth.
molecular
events
controlling
integrity
that
facilitate
the
development
hepatocellular
carcinoma
(HCC)
remain
unclear.
Here,
we
report
UBX
domain-containing
protein
1
(UBXN1)
hyperactivation
essential
liver
tumorigenesis.
Language: Английский
PGC-1α drives small cell neuroendocrine cancer progression toward an ASCL1-expressing subtype with increased mitochondrial capacity
Grigor Varuzhanyan,
No information about this author
Chia‐Chun Chen,
No information about this author
Jack Freeland
No information about this author
et al.
Proceedings of the National Academy of Sciences,
Journal Year:
2024,
Volume and Issue:
121(49)
Published: Nov. 26, 2024
Adenocarcinomas
from
multiple
tissues
can
converge
to
treatment-resistant
small
cell
neuroendocrine
(SCN)
cancers
composed
of
ASCL1,
POU2F3,
NEUROD1,
and
YAP1
subtypes.
We
investigated
how
mitochondrial
metabolism
influences
SCN
cancer
(SCNC)
progression.
Extensive
bioinformatics
analyses
encompassing
thousands
patient
tumors
human
lines
uncovered
enhanced
expression
proliferator-activatedreceptor
gamma
coactivator
1-alpha
(PGC-1α),
a
potent
regulator
oxidative
phosphorylation
(OXPHOS),
across
several
SCNCs.
PGC-1α
correlated
tightly
with
increased
the
lineage
marker
Achaete-scute
homolog
1,
(ASCL1)
through
positive
feedback
mechanism.
Analyses
using
prostate
tissue-based
transformation
system
showed
that
ASCL1
subtype
has
heightened
OXPHOS
activity.
inhibition
diminished
OXPHOS,
reduced
SCNC
proliferation,
blocked
tumor
formation.
Conversely,
overexpression
validated
by
small-animal
Positron
Emission
Tomography
imaging,
tripled
formation
rate,
promoted
commitment
lineage.
These
results
establish
as
driver
progression
determination,
highlighting
metabolic
vulnerabilities
in
SCNCs
different
tissues.
Language: Английский
Personalized Medicine: Leave no Patient Behind; Report From the 2024 Coffey‐Holden Prostate Cancer Academy Meeting
The Prostate,
Journal Year:
2024,
Volume and Issue:
85(3), P. 211 - 226
Published: Nov. 27, 2024
ABSTRACT
Introduction
The
11th
Annual
2024
Coffey
‐
Holden
Prostate
Cancer
Academy
(CHPCA)
Meeting,
was
themed
“Personalized
Medicine:
Leave
No
Patient
Behind,”
and
held
from
June
20
to
23,
at
the
University
of
California,
Los
Angeles,
Luskin
Conference
Center,
in
CA.
Methods
CHPCA
Meeting
is
an
academy‐styled
annual
conference
organized
by
Foundation,
focus
discussion
on
most
critical
emerging
research
that
have
greatest
potential
advance
knowledge
prostate
cancer
biology
treatment.
attended
75
academic
investigators
included
37
talks
across
8
sessions.
Results
meeting
sessions
focused
on:
novel
human,
mouse
systems
models,
immunotherapies
for
cancer,
efforts
overcome
treatment
resistance,
role
metabolism
diet
as
a
therapeutic
target,
mechanisms
drive
differentiation
into
neuroendocrine
subtypes,
evolving
epigenome
disease
progression
machine
learning
advanced
computational
approaches
precision
oncology.
Discussion
This
article
summarizes
presentations
discussions
Meeting.
We
hope
sharing
this
will
inspire
accelerate
new
discoveries
solutions
cancer.
Language: Английский