Cancer Research,
Journal Year:
2022,
Volume and Issue:
82(24), P. 4555 - 4570
Published: Oct. 10, 2022
Abstract
Tumor
heterogeneity
is
a
key
feature
of
melanomas
that
hinders
development
effective
treatments.
Aiming
to
overcome
this,
we
identified
LINC00518
(LENOX;
lincRNA-enhancer
oxidative
phosphorylation)
as
melanoma-specific
lncRNA
expressed
in
all
known
melanoma
cell
states
and
essential
for
survival
vitro
vivo.
Mechanistically,
LENOX
promoted
association
the
RAP2C
GTPase
with
mitochondrial
fission
regulator
DRP1,
increasing
DRP1
S637
phosphorylation,
fusion,
phosphorylation.
expression
was
upregulated
following
treatment
MAPK
inhibitors,
facilitating
metabolic
switch
from
glycolysis
phosphorylation
conferring
resistance
inhibition.
Consequently,
combined
silencing
synergized
inhibitors
eradicate
cells.
Melanomas
are
thus
addicted
LENOX,
which
acts
optimize
function
during
progression.
Significance:
The
novel
metabolism,
can
be
targeted
conjunction
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: March 20, 2023
Metabolic
abnormalities
lead
to
the
dysfunction
of
metabolic
pathways
and
metabolite
accumulation
or
deficiency
which
is
well-recognized
hallmarks
diseases.
Metabolite
signatures
that
have
close
proximity
subject's
phenotypic
informative
dimension,
are
useful
for
predicting
diagnosis
prognosis
diseases
as
well
monitoring
treatments.
The
lack
early
biomarkers
could
poor
serious
outcomes.
Therefore,
noninvasive
methods
with
high
specificity
selectivity
desperately
needed.
Small
molecule
metabolites-based
metabolomics
has
become
a
specialized
tool
biomarker
pathway
analysis,
revealing
possible
mechanisms
human
various
deciphering
therapeutic
potentials.
It
help
identify
functional
related
variation
delineate
biochemical
changes
indicators
pathological
damage
prior
disease
development.
Recently,
scientists
established
large
number
profiles
reveal
underlying
networks
target
exploration
in
biomedicine.
This
review
summarized
analysis
on
potential
value
small-molecule
candidate
metabolites
clinical
events,
may
better
diagnosis,
prognosis,
drug
screening
treatment.
We
also
discuss
challenges
need
be
addressed
fuel
next
wave
breakthroughs.
Nature,
Journal Year:
2022,
Volume and Issue:
607(7919), P. 593 - 603
Published: June 29, 2022
Aggressive
and
metastatic
cancers
show
enhanced
metabolic
plasticity1,
but
the
precise
underlying
mechanisms
of
this
remain
unclear.
Here
we
how
two
NOP2/Sun
RNA
methyltransferase
3
(NSUN3)-dependent
modifications-5-methylcytosine
(m5C)
its
derivative
5-formylcytosine
(f5C)
(refs.2-4)-drive
translation
mitochondrial
mRNA
to
power
metastasis.
Translation
mitochondrially
encoded
subunits
oxidative
phosphorylation
complex
depends
on
formation
m5C
at
position
34
in
tRNAMet.
m5C-deficient
human
oral
cancer
cells
exhibit
increased
levels
glycolysis
changes
their
function
that
do
not
affect
cell
viability
or
primary
tumour
growth
vivo;
however,
plasticity
is
severely
impaired
as
tumours
metastasize
efficiently.
We
discovered
CD36-dependent
non-dividing,
metastasis-initiating
require
activate
invasion
dissemination.
Moreover,
a
mitochondria-driven
gene
signature
patients
with
head
neck
predictive
for
metastasis
disease
progression.
Finally,
confirm
switch
allows
can
be
pharmacologically
targeted
through
inhibition
vivo.
Together,
our
results
reveal
site-specific
modifications
could
therapeutic
targets
combat
Cell Communication and Signaling,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: Feb. 1, 2024
Colorectal
cancer
(CRC)
is
a
significant
public
health
concern,
and
its
development
associated
with
mitochondrial
dysfunction.
Mitochondria
can
adapt
to
the
high
metabolic
demands
of
cells
owing
their
plasticity
dynamic
nature.
The
fusion-fission
dynamics
mitochondria
play
crucial
role
in
signal
transduction
functions
CRC
cells.
Enhanced
fission
promotes
reprogramming
cells,
leading
cell
proliferation,
metastasis,
chemoresistance.
Excessive
also
trigger
mitochondria-mediated
apoptosis.
In
contrast,
excessive
fusion
leads
adenosine
triphosphate
(ATP)
overproduction
abnormal
tumor
whereas
moderate
protects
intestinal
epithelial
from
oxidative
stress-induced
damage,
thus
preventing
colitis-associated
(CAC).
Therefore,
an
imbalance
either
promote
or
inhibit
progression.
This
review
provides
overview
mechanism
underlying
impact
on
biology.
revealed
dual
identified
potential
drug
targets.
Additionally,
this
study
partially
explored
immune
vascular
endothelial
microenvironment,
suggesting
promising
prospects
for
targeting
key
fusion/fission
effector
proteins
against
CRC.
Cell Metabolism,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 1, 2025
Tumors
arise
from
uncontrolled
cell
proliferation
driven
by
mutations
in
genes
that
regulate
stem
renewal
and
differentiation.
Intestinal
tumors,
however,
retain
some
hierarchical
organization,
maintaining
both
cancer
cells
(CSCs)
differentiated
(CDCs).
This
heterogeneity,
coupled
with
cellular
plasticity
enabling
CDCs
to
revert
CSCs,
contributes
therapy
resistance
relapse.
Using
genetically
encoded
fluorescent
reporters
human
tumor
organoids,
combined
our
machine-learning-based
tracker,
CellPhenTracker,
we
simultaneously
traced
cell-type
specification,
metabolic
changes,
reconstructed
lineage
trajectories
during
organoid
development.
Our
findings
reveal
distinctive
phenotypes
CSCs
CDCs.
We
find
lactate
regulates
dynamics,
suppressing
CSC
differentiation
inducing
dedifferentiation
into
a
proliferative
state.
Mechanistically,
increases
histone
acetylation,
epigenetically
activating
MYC.
Given
lactate's
regulation
of
MYC
depends
on
the
bromodomain-containing
protein
4
(BRD4),
targeting
metabolism
BRD4
inhibitors
emerge
as
promising
strategy
prevent
Current Opinion in Neurobiology,
Journal Year:
2021,
Volume and Issue:
69, P. 231 - 240
Published: June 23, 2021
Neural
stem
cells
(NSCs)
undergo
massive
molecular
and
cellular
changes
during
neuronal
differentiation.
These
include
mitochondria
metabolism
remodelling,
which
were
thought
to
be
mostly
permissive
cues,
but
recent
work
indicates
that
they
are
causally
linked
neurogenesis.
Striking
remodelling
of
occurs
right
after
mitosis
NSCs,
influences
the
postmitotic
daughter
towards
self-renewal
or
The
transitioning
fate
requires
metabolic
rewiring
including
increased
oxidative
phosphorylation
activity,
drives
transcriptional
epigenetic
effects
influence
cell
fate.
Mitochondria
pathways
also
contribute
in
an
essential
way
regulation
NSC
proliferation
self-renewal.
on
neurogenesis
is
conserved
from
fly
human
systems,
displays
striking
differences
context
species.
new
findings
have
important
implications
for
our
understanding
neurodevelopmental
diseases
possibly
brain
evolution.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: July 25, 2022
Abstract
Mitochondria
are
highly
dynamic
organelles
whose
fragmentation
by
fission
is
critical
to
their
functional
integrity
and
cellular
homeostasis.
Here,
we
develop
a
method
via
optogenetic
control
of
mitochondria–lysosome
contacts
(MLCs)
induce
mitochondrial
with
spatiotemporal
accuracy.
MLCs
can
be
achieved
blue-light-induced
association
mitochondria
lysosomes
through
various
photoactivatable
dimerizers.
Real-time
induction
tracked
in
living
cells
measure
the
rate.
The
partially
restores
functions
SLC25A46
−/−
cells,
which
display
defects
hyperfused
mitochondria.
system
thus
provides
platform
for
studying
treating
diseases.