Nature Genetics,
Год журнала:
2022,
Номер
54(12), С. 1827 - 1838
Опубликована: Сен. 29, 2022
Abstract
We
identify
the
sodium
leak
channel
non-selective
protein
(NALCN)
as
a
key
regulator
of
cancer
metastasis
and
nonmalignant
cell
dissemination.
Among
10,022
human
cancers,
NALCN
loss-of-function
mutations
were
enriched
in
gastric
colorectal
cancers.
Deletion
Nalcn
from
gastric,
intestinal
or
pancreatic
adenocarcinomas
mice
did
not
alter
tumor
incidence,
but
markedly
increased
number
circulating
cells
(CTCs)
metastases.
Treatment
these
with
gadolinium—a
blocker—similarly
CTCs
that
lacked
oncogenic
never
developed
caused
shedding
epithelial
into
blood
at
levels
equivalent
to
those
seen
tumor-bearing
animals.
These
trafficked
distant
organs
form
normal
structures
including
lung
epithelium,
kidney
glomeruli
tubules.
Thus,
regulates
solid
tissues
independent
cancer,
divorcing
this
process
tumorigenesis
unmasking
potential
new
target
for
antimetastatic
therapies.
Signal Transduction and Targeted Therapy,
Год журнала:
2021,
Номер
6(1)
Опубликована: Авг. 30, 2021
Ribosome
biogenesis
and
protein
synthesis
are
fundamental
rate-limiting
steps
for
cell
growth
proliferation.
The
ribosomal
proteins
(RPs),
comprising
the
structural
parts
of
ribosome,
essential
ribosome
assembly
function.
In
addition
to
their
canonical
functions,
multiple
RPs
have
extra-ribosomal
functions
including
activation
p53-dependent
or
p53-independent
pathways
in
response
stress,
resulting
cycle
arrest
apoptosis.
Defects
biogenesis,
translation,
individual
RPs,
mutations
been
linked
a
diverse
range
human
congenital
disorders
termed
ribosomopathies.
Ribosomopathies
characterized
by
tissue-specific
phenotypic
abnormalities
higher
cancer
risk
later
life.
Recent
discoveries
somatic
tumor
types
reinforce
connections
between
defects
cancer.
this
article,
we
review
most
recent
advances
understanding
molecular
consequences
RP
ribosomopathies
We
particularly
discuss
basis
transition
from
hypo-
hyper-proliferation
with
elevated
risk,
paradox
"Dameshek's
riddle."
Furthermore,
current
treatments
prospective
therapies
targeting
defects.
also
highlight
stress-based
therapeutics.
Importantly,
insights
into
mechanisms
resistance
bring
new
perspectives
susceptibility
clinical
implications
therapy.
International Journal of Cancer,
Год журнала:
2020,
Номер
148(3), С. 528 - 545
Опубликована: Июль 19, 2020
The
analysis
of
tumor
cells
or
cell
products
obtained
from
blood
other
body
fluids
("liquid
biopsy"
[LB])
provides
a
broad
range
opportunities
in
the
field
oncology.
Clinical
application
areas
include
early
detection
cancer
recurrence,
individual
risk
assessment
and
therapy
monitoring.
LB
allows
to
portray
entire
disease
as
are
released
all
metastatic
primary
sites,
providing
comprehensive
real-time
information
on
evolution,
therapeutic
targets
mechanisms
resistance
therapy.
Here,
we
focus
most
prominent
markers,
circulating
(CTCs)
tumor-derived
DNA
(ctDNA),
patients
with
breast,
prostate,
lung
colorectal
cancer,
four
frequent
types
Europe.
After
brief
introduction
key
technologies
used
detect
CTCs
ctDNA,
discuss
recent
clinical
studies
these
biomarkers
for
prognostication
well
prediction
monitoring
therapies.
We
also
point
out
current
methodological
biological
limitations
that
still
hamper
implementation
into
practice.
Cancer Research,
Год журнала:
2022,
Номер
82(13), С. 2344 - 2353
Опубликована: Март 18, 2022
Abstract
Ribosomes
are
a
complex
ensemble
of
rRNA
and
ribosomal
proteins
that
function
as
mRNA
translation
machines.
Ribosome
biogenesis
is
multistep
process
begins
in
the
nucleolus
concludes
cytoplasm.
The
tightly
controlled
by
multiple
checkpoint
surveillance
pathways.
Perturbations
these
checkpoints
pathways
can
lead
to
hyperactivation
ribosome
biogenesis.
Emerging
evidence
suggests
cancer
cells
harbor
specialized
class
ribosomes
(onco-ribosomes)
facilitates
oncogenic
program,
modulates
cellular
functions,
promotes
metabolic
rewiring.
Mutations
proteins,
processing,
assembly
factors
result
ribosomopathies
associated
with
an
increased
risk
developing
malignancies.
Recent
studies
have
linked
mutations
aberrant
poor
prognosis,
highlighting
ribosome-targeted
therapy
promising
approach
for
treating
patients
cancer.
Here,
we
summarize
various
aspects
dysregulation
impact
resultant
onco-ribosomes
on
malignant
tumor
behavior,
therapeutic
resistance,
clinical
outcome.
target,
understanding
important
determinants
this
will
allow
improved
perhaps
selective
strategies
target
biosynthesis.
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(11), С. 5496 - 5496
Опубликована: Май 23, 2021
Cytosolic
ribosomes
(cytoribosomes)
are
macromolecular
ribonucleoprotein
complexes
that
assembled
from
ribosomal
RNA
and
proteins,
which
essential
for
protein
biosynthesis.
Mitochondrial
(mitoribosomes)
perform
translation
of
the
proteins
oxidative
phosphorylation
system.
The
biogenesis
cytoribosomes
mitoribosomes
includes
processing,
modification
binding
to
is
assisted
by
numerous
factors.
This
a
major
energy-consuming
process
in
cell
and,
therefore,
highly
coordinated
sensitive
several
cellular
stressors.
In
mitochondria,
regulation
mitoribosome
respiration,
linked
growth
proliferation.
review
briefly
overviews
key
stages
cytosolic
mitochondrial
ribosome
biogenesis;
summarizes
main
steps
alterations
occurring
during
tumorigenesis,
highlighting
changes
expression
level
(CRPs)
(MRPs)
different
types
tumors;
focuses
on
currently
available
information
regarding
extra-ribosomal
functions
CRPs
MRPs
correlated
cancer;
discusses
role
as
biomarkers
and/or
molecular
targets
cancer
treatment.
