Cell Death Discovery,
Journal Year:
2025,
Volume and Issue:
11(1)
Published: Feb. 20, 2025
Recent
progress
in
cancer
metabolism
research
has
identified
lactylation
as
a
critical
post-translational
modification
influencing
tumor
development
and
progression.
The
process
relies
on
lactate
accumulation
the
activation
of
lactate-sensitive
acyltransferases.
Beyond
its
role
epigenetic
regulation,
emerged
significant
factor
evolution,
offering
fresh
opportunities
for
developing
targeted
therapies
that
transcend
traditional
approaches.
This
review
explores
growing
importance
biology
highlights
potential
advancing
diagnostic
tools
therapeutic
strategies.
Nature Reviews Drug Discovery,
Journal Year:
2022,
Volume and Issue:
21(4), P. 283 - 305
Published: Jan. 14, 2022
Fatty
acids
are
essential
for
survival,
acting
as
bioenergetic
substrates,
structural
components
and
signalling
molecules.
Given
their
vital
role,
cells
have
evolved
mechanisms
to
generate
fatty
from
alternative
carbon
sources,
through
a
process
known
de
novo
lipogenesis
(DNL).
Despite
the
importance
of
DNL,
aberrant
upregulation
is
associated
with
wide
variety
pathologies.
Inhibiting
core
enzymes
including
citrate/isocitrate
carrier
(CIC),
ATP-citrate
lyase
(ACLY),
acetyl-CoA
carboxylase
(ACC)
acid
synthase
(FAS),
represents
an
attractive
therapeutic
strategy.
challenges
related
efficacy,
selectivity
safety,
several
new
classes
synthetic
DNL
inhibitors
entered
clinical-stage
development
may
become
foundation
class
therapeutics.
De
(DNL)
maintenance
whole-body
cellular
homeostasis,
but
pathway
broad
range
conditions,
cardiovascular
disease,
metabolic
disorders
cancers.
Here,
Steinberg
colleagues
provide
overview
physiological
pathological
roles
assess
strategies
agents
currently
in
therapeutically
target
them.
Journal of Hematology & Oncology,
Journal Year:
2022,
Volume and Issue:
15(1)
Published: Aug. 29, 2022
Circular
RNAs
(circRNAs)
represent
a
novel
type
of
regulatory
RNA
characterized
by
high
evolutionary
conservation
and
stability.
CircRNAs
are
expected
to
be
potential
diagnostic
biomarkers
therapeutic
targets
for
variety
malignancies.
However,
the
functions
underlying
mechanisms
circRNAs
in
triple-negative
breast
cancer
(TNBC)
largely
unknown.
Nucleic Acids Research,
Journal Year:
2021,
Volume and Issue:
50(D1), P. D719 - D728
Published: Oct. 6, 2021
Abstract
As
an
important
post-translational
modification,
ubiquitination
mediates
∼80%
of
protein
degradation
in
eukaryotes.
The
degree
is
tightly
determined
by
the
delicate
balance
between
specific
ubiquitin
ligase
(E3)-mediated
and
deubiquitinase-mediated
deubiquitination.
In
2017,
we
developed
UbiBrowser
1.0,
which
integrated
database
for
predicted
human
proteome-wide
E3–substrate
interactions.
Here,
to
meet
urgent
requirement
E3/deubiquitinase–substrate
interactions
(ESIs/DSIs)
multiple
organisms,
updated
version
2.0
(http://ubibrowser.ncpsb.org.cn).
Using
improved
protocol,
collected
4068/967
known
ESIs/DSIs
manual
curation,
about
2.2
million
highly
confident
39
with
>210-fold
increase
total
data
volume.
addition,
made
several
new
features
version:
(i)
it
allows
exploring
proteins’
upstream
E3
ligases
deubiquitinases
simultaneously;
(ii)
has
significantly
increased
species
coverage;
(iii)
presents
a
uniform
confidence
scoring
system
rank
ESIs/DSIs.
To
facilitate
usage
2.0,
also
redesigned
web
interface
these
ESIs/DSIs,
added
functions
‘Browse’,
‘Download’
‘Application
Programming
Interface’.
We
believe
that
as
discovery
tool,
will
contribute
study
development
drug
targets
complex
diseases.
Molecular Cancer,
Journal Year:
2024,
Volume and Issue:
23(1)
Published: July 25, 2024
Abstract
Ubiquitination,
a
pivotal
posttranslational
modification
of
proteins,
plays
fundamental
role
in
regulating
protein
stability.
The
dysregulation
ubiquitinating
and
deubiquitinating
enzymes
is
common
feature
various
cancers,
underscoring
the
imperative
to
investigate
ubiquitin
ligases
deubiquitinases
(DUBs)
for
insights
into
oncogenic
processes
development
therapeutic
interventions.
In
this
review,
we
discuss
contributions
ubiquitin–proteasome
system
(UPS)
all
hallmarks
cancer
progress
drug
discovery.
We
delve
multiple
functions
UPS
oncology,
including
its
regulation
cancer-associated
pathways,
metabolic
reprogramming,
engagement
with
tumor
immune
responses,
function
phenotypic
plasticity
polymorphic
microbiomes,
other
essential
cellular
functions.
Furthermore,
provide
comprehensive
overview
novel
anticancer
strategies
that
leverage
UPS,
application
proteolysis
targeting
chimeras
(PROTACs)
molecular
glues.
Cancers,
Journal Year:
2025,
Volume and Issue:
17(2), P. 248 - 248
Published: Jan. 14, 2025
The
epidermal
growth
factor
receptor
(EGFR)
regulates
gene
expression
through
two
primary
mechanisms:
as
a
in
the
nucleus,
where
it
translocates
upon
binding
its
ligand,
or
via
intrinsic
tyrosine
kinase
activity
cytosol,
modulates
key
signaling
pathways
such
RAS/MYC,
PI3K,
PLCγ,
and
STAT3.
During
tumorigenesis,
these
become
deregulated,
leading
to
uncontrolled
proliferation,
enhanced
migratory
metastatic
capabilities,
evasion
of
programmed
cell
death,
resistance
chemotherapy
radiotherapy.
RAS
MYC
oncogenes
are
pivotal
driving
processes
apoptosis,
replicative
immortality,
cellular
invasion
metastasis,
metabolic
reprogramming.
These
subject
regulation
by
range
epigenetic
post-transcriptional
modifications.
This
review
focuses
on
deregulation
EGFR,
RAS,
caused
(epi)genetic
alterations
post-translational
It
also
explores
therapeutic
potential
targeting
regulatory
proteins,
emphasizing
importance
phenotyping
neoplastic
tissues
inform
treatment
cancer.
Life,
Journal Year:
2025,
Volume and Issue:
15(1), P. 126 - 126
Published: Jan. 18, 2025
Post-translational
modifications
(PTMs)
of
proteins
dynamically
build
the
buffering
and
adapting
interface
between
oncogenic
mutations
environmental
stressors,
on
one
hand,
cancer
cell
structure,
functioning,
behavior.
Aberrant
PTMs
can
be
considered
as
enabling
characteristics
long
they
orchestrate
all
malignant
variability
in
proteome
cells,
cancer-associated
tumor
microenvironment
(TME).
On
other
enhance
anticancer
mechanisms
tumoral
ecosystem
or
sustain
beneficial
effects
oncologic
therapies
through
degradation
inactivation
carcinogenic
or/and
activation
tumor-suppressor
proteins.
In
this
review,
we
summarized
analyzed
a
wide
spectrum
involved
regulatory
that
drive
tumorigenesis,
genetic
instability,
epigenetic
reprogramming,
events
metastatic
cascade,
cytoskeleton
extracellular
matrix
(ECM)
remodeling,
angiogenesis,
immune
response,
tumor-associated
microbiome,
metabolism
rewiring
most
important
hallmarks
cancer.
All
develop
due
to
proteins,
which
modulate
gene
transcription,
intracellular
signaling,
protein
size,
activity,
stability
localization,
trafficking,
secretion,
half-life,
protein–protein
interactions
(PPIs).
associated
with
exploited
better
understand
underlying
molecular
heterogeneous
chameleonic
disease,
find
new
biomarkers
progression
prognosis,
personalize
oncotherapies,
discover
targets
for
drug
development.
Cells,
Journal Year:
2021,
Volume and Issue:
10(11), P. 2944 - 2944
Published: Oct. 29, 2021
Bone
and
bone
marrow
are
among
the
most
frequent
metastatic
sites
of
cancer.
The
occurrence
metastasis
is
frequently
associated
with
a
dismal
disease
outcome.
prevention
therapy
metastases
priority
in
treatment
cancer
patients.
However,
current
therapeutic
options
for
patients
limited
efficacy
increased
morbidity.
Therefore,
therapies
mainly
palliative
nature.
A
better
understanding
underlying
molecular
pathways
process
warranted
to
develop
novel,
well-tolerated
more
successful
treatments
significant
improvement
patients’
quality
life
In
this
review,
we
provide
comparative
mechanistic
insights
into
various
solid
tumors,
including
pediatric
cancers.
We
also
highlight
innovative
approaches
biologically
targeted
immunotherapy.
particular,
discuss
role
microenvironment
attraction,
homing,
dormancy
outgrowth
tumor
cells
ensuing
implications.
Multiple
signaling
have
been
described
contribute
spread
specific
entities,
knowledge
derived
from
study
breast
prostate
it
likely
that
similar
mechanisms
involved
different
types
cancer,
multiple
myeloma,
primary
sarcomas
neuroblastoma.
rate-limiting
interaction
cellular
noncellular
components
bone-marrow
niche
provides
attractive
targets,
which
already
partially
exploited
by
novel
promising
immunotherapies.
Molecules,
Journal Year:
2022,
Volume and Issue:
27(15), P. 4818 - 4818
Published: July 27, 2022
Cancer
is
the
second
leading
cause
of
death
after
cardiovascular
diseases.
Conventional
anticancer
therapies
are
associated
with
lack
selectivity
and
serious
side
effects.
hallmarks
biological
capabilities
acquired
by
cancer
cells
during
neoplastic
transformation.
Targeting
multiple
a
promising
strategy
to
treat
cancer.
The
diversity
in
chemical
structure
relatively
low
toxicity
make
plant-derived
natural
products
source
for
development
new
more
effective
that
have
capacity
target
In
this
review,
we
discussed
activities
ten
extracted
from
plants.
majority
these
inhibit
targeting
hallmarks,
many
chemicals
reached
clinical
applications.
Studies
review
provide
solid
ground
researchers
physicians
design
combination
using
products.
Cells,
Journal Year:
2023,
Volume and Issue:
13(1), P. 29 - 29
Published: Dec. 22, 2023
Ubiquitination
is
a
reversible
post-translational
modification
based
on
the
chemical
addition
of
ubiquitin
to
proteins
with
regulatory
effects
various
signaling
pathways.
can
alter
molecular
functions
tagged
substrates
respect
protein
turnover,
biological
activity,
subcellular
localization
or
protein–protein
interaction.
As
result,
wide
variety
cellular
processes
are
under
ubiquitination-mediated
control,
contributing
maintenance
homeostasis.
It
follows
that
dysregulation
ubiquitination
reactions
plays
relevant
role
in
pathogenic
states
human
diseases
such
as
neurodegenerative
diseases,
immune-related
pathologies
and
cancer.
In
recent
decades,
enzymes
ubiquitin–proteasome
system
(UPS),
including
E3
ligases
deubiquitinases
(DUBs),
have
attracted
attention
novel
druggable
targets
for
development
new
anticancer
therapeutic
approaches.
This
perspective
article
summarizes
peculiarities
shared
by
involved
reaction
which,
when
deregulated,
lead
tumorigenesis.
Accordingly,
an
overview
main
pharmacological
interventions
targeting
UPS
clinical
use
still
trials
provided,
also
highlighting
limitations
efficacy
these
Therefore,
attempts
circumvent
drug
resistance
side
well
UPS-related
emerging
technologies
therapeutics
discussed.
