Metabolites,
Journal Year:
2023,
Volume and Issue:
13(3), P. 331 - 331
Published: Feb. 23, 2023
The
small
molecule
citrate
is
a
key
that
synthesized
de
novo
and
involved
in
diverse
biochemical
pathways
influencing
cell
metabolism
function.
Citrate
highly
abundant
the
circulation,
cells
take
up
extracellular
via
sodium-dependent
plasma
membrane
transporter
NaCT
encoded
by
SLC13A5
gene.
critical
to
maintaining
metabolic
homeostasis
impaired
activity
implicated
disorders.
Though
one
of
best
known
most
studied
metabolites
humans,
little
about
consequences
altered
uptake
metabolism.
Here,
we
review
recent
findings
on
SLC13A5,
NaCT,
discuss
effects
SLC13A5-dependent
phenotypes.
We
“multiple-hit
theory”
how
stress
factors
induce
reprogramming
may
synergize
with
alter
fate
Furthermore,
underline
compartmentalization
can
be
quantified
combining
mass
spectrometry
tracing
approaches.
also
species-specific
differences
potential
therapeutic
implications
NaCT.
Understanding
synergistic
impact
multiple
help
decipher
disease
mechanisms
associated
transport
International Journal of Cancer,
Journal Year:
2024,
Volume and Issue:
155(1), P. 27 - 39
Published: March 2, 2024
Abstract
Information
about
the
NMR
metabolomics
landscape
of
overall,
and
common
cancers
is
still
limited.
Based
on
a
cohort
83,290
participants
from
UK
Biobank,
we
used
multivariate
Cox
regression
to
assess
associations
between
each
168
metabolites
with
risks
overall
cancer
20
specific
types
cancer.
Then,
applied
LASSO
identify
important
for
risk
obtained
their
using
cox
regression.
We
further
conducted
mediation
analysis
evaluate
mediated
role
in
effects
traditional
factors
risk.
Finally,
included
13
identified
as
predictors
prediction
models,
compared
accuracies
our
models.
found
that
there
were
commonalities
among
metabolic
profiles
cancer:
top
frequently
all
associated
cancer;
most
had
metabolites.
Meanwhile,
same
metabolite
different
can
vary
based
site
origin.
biomarkers
cancer,
they
factors.
The
models
improved
when
added
This
study
helpful
understand
mechanisms
wide
range
cancers,
results
also
indicate
are
potential
diagnosis
prevention.
The
liver,
characterized
by
a
unique
metabolic
and
immunosuppressive
environment,
is
also
the
organ
to
which
invasive
malignant
cells
of
many
different
cancer
types
most
frequently
metastasize.
reasons
for
this
organ-specific
metastatic
process
have
been
investigated
decades.
This
review
first
provides
an
overview
recent
breakthroughs
in
field,
introducing
intercellular
communication
between
circulating
tumor
heterogeneous
cell
populations
modifications
extracellular
matrix
(ECM).
Subsequently,
improve
understanding
molecular
mechanisms
involved
metastasis
colorectal
second
leading
cause
cancer-related
mortality,
literature
on
question
was
analyzed.
Among
various
parameters
involved,
behind
activation
hepatic
stellate
cells,
proteins
inducing
ECM
remodeling,
specific
genomic
features
liver
metastases,
rewiring,
characteristics
stromal-enriched
microenvironments
were
discussed.
To
provide
more
insights
into
determinants
colonization,
important
findings
reported
set
mitochondrial
addressed,
relative
abundance
changed
during
progression
stage
aggressive
experimental
model
peritoneal
mesothelioma
immunocompetent
rats.
Based
previous
studies
cross-comparing
proteomes
from
curcumin-treated
tumor-bearing
rats/untreated
rats/normal
rats,
data
reviewed
25
interest.
Their
role
lipid
metabolism,
heme
biosynthesis,
electron
transport
chain,
small
molecule
transport,
dynamics,
tricarboxylic
acid
cycle,
protection
against
oxidative
stress
analyzed
context
both
non-malignant
diseases.
Frontiers in Cell and Developmental Biology,
Journal Year:
2024,
Volume and Issue:
12
Published: July 3, 2024
We
have
recently
shown
that
cancer
cells
of
various
origins
take
up
extracellular
citrate
through
the
plasma
membrane
carrier
(pmCiC),
a
specific
transporter.
Extracellular
is
required
to
support
cell
metabolism,
in
particular
fatty
acid
synthesis,
mitochondrial
activity,
protein
synthesis
and
histone
acetylation.
In
addition,
tend
acquire
metastatic
phenotype
presence
citrate.
Our
recent
study
also
showed
cancer-associated
stromal
synthesise
release
this
process
controlled
by
cells.
present
study,
we
evaluated
expression
pmCiC,
fibroblast
activation
protein-α
(FAP)
angiogenesis
marker
cluster
differentiation
31
(CD31)
human
tissues
different
origins.
cohort
studied,
found
no
correlation
between
disease
stage
FAP
or
CD31.
However,
identified
clear
pmCiC
stroma
with
tumour
stage.
It
can
be
concluded
increased
cancer-supporting
microenvironment
at
later
stages
development,
particularly
sites.
Therefore,
has
potential
serve
as
prognostic
marker,
although
further
studies
are
needed.
Cancer & Metabolism,
Journal Year:
2024,
Volume and Issue:
12(1)
Published: Nov. 19, 2024
Glioblastoma
is
an
aggressive
cancer
that
originates
from
abnormal
cell
growth
in
the
brain
and
requires
metabolic
reprogramming
to
support
tumor
growth.
Metabolic
involves
upregulation
of
various
pathways.
Although
activation
specific
pathways
glioblastoma
lines
has
been
documented,
comprehensive
profile
role
each
pathway
tissues
patients
remain
elusive.
We
analyzed
38
tissues.
As
a
test
set,
we
examined
20
Kyushu
University
Hospital,
focusing
on
proteins
related
several
pathways,
including
glycolysis,
one-carbon
cycle,
glutaminolysis,
mitochondrial
tricarboxylic
acid
cycle.
Subsequently,
additional
18
Kagoshima
Hospital
as
validation
set.
also
validated
our
findings
using
six
lines,
U87,
LN229,
U373,
T98G,
two
patient-derived
cells.
The
levels
mitochondria-related
(COX1,
COX2,
DRP1)
were
correlated
with
other
glutaminolysis-related
(GLDH
GLS1).
Conversely,
their
expression
was
inversely
glycolytic
proteins.
Notably,
inhibiting
glutaminolysis
high
GLDH
GLS1
proved
effective
suppressing
Our
confirm
can
be
categorized
into
glycolytic-dominant
mitochondrial-dominant
types,
previously
reported.
type
glutaminolysis-dominant.
Therefore,
may
treatment
for
glioblastoma.
Metabolites,
Journal Year:
2023,
Volume and Issue:
13(3), P. 331 - 331
Published: Feb. 23, 2023
The
small
molecule
citrate
is
a
key
that
synthesized
de
novo
and
involved
in
diverse
biochemical
pathways
influencing
cell
metabolism
function.
Citrate
highly
abundant
the
circulation,
cells
take
up
extracellular
via
sodium-dependent
plasma
membrane
transporter
NaCT
encoded
by
SLC13A5
gene.
critical
to
maintaining
metabolic
homeostasis
impaired
activity
implicated
disorders.
Though
one
of
best
known
most
studied
metabolites
humans,
little
about
consequences
altered
uptake
metabolism.
Here,
we
review
recent
findings
on
SLC13A5,
NaCT,
discuss
effects
SLC13A5-dependent
phenotypes.
We
“multiple-hit
theory”
how
stress
factors
induce
reprogramming
may
synergize
with
alter
fate
Furthermore,
underline
compartmentalization
can
be
quantified
combining
mass
spectrometry
tracing
approaches.
also
species-specific
differences
potential
therapeutic
implications
NaCT.
Understanding
synergistic
impact
multiple
help
decipher
disease
mechanisms
associated
transport
