Journal of Extracellular Vesicles,
Год журнала:
2021,
Номер
10(11)
Опубликована: Сен. 1, 2021
Cancer-associated
fibroblasts
(CAFs)
as
a
predominant
cell
component
in
the
tumour
microenvironment
(TME)
play
an
essential
role
progression.
Our
earlier
studies
revealed
oxidized
ATM
activation
breast
CAFs,
which
is
independent
of
DNA
double-strand
breaks
(DSBs).
Oxidized
has
been
found
to
serve
redox
sensor
maintain
cellular
homeostasis.
However,
whether
and
how
CAFs
regulates
cancer
progression
remains
poorly
understood.
In
this
study,
we
that
phosphorylates
BNIP3
induce
autophagosome
accumulation
exosome
release
from
hypoxic
CAFs.
Inhibition
kinase
by
KU60019
(a
small-molecule
inhibitor
activated
ATM)
or
shRNA-mediated
knockdown
endogenous
blocks
autophagy
We
also
show
ATP6V1G1,
core
proton
pump
maintaining
lysosomal
acidification,
leading
dysfunction
fusion
with
multi-vesicular
bodies
(MVB)
but
not
lysosomes
facilitate
release.
Furthermore,
autophagy-associated
GPR64
enriched
CAFs-derived
exosomes,
stimulates
non-canonical
NF-κB
signalling
upregulate
MMP9
IL-8
recipient
cells,
enabling
cells
acquire
enhanced
invasive
abilities.
Collectively,
these
results
provide
novel
insights
into
stromal
promoting
reveal
new
function
regulating
FEBS Journal,
Год журнала:
2022,
Номер
290(5), С. 1362 - 1383
Опубликована: Янв. 11, 2022
The
concept
of
geroscience
is
that
since
ageing
the
greatest
risk
factor
for
many
diseases
and
conditions,
targeting
process
itself
will
have
impact
on
human
health.
Of
hallmarks
ageing,
cellular
senescence
has
emerged
as
a
druggable
therapeutic
target
extending
healthspan
in
model
organisms.
Cellular
cell
state
irreversible
proliferative
arrest
driven
by
different
types
stress,
including
oncogene‐induced
stress.
Many
senescent
cells
(SnCs)
develop
senescent‐associated
secretory
phenotype
(SASP)
comprising
pro‐inflammatory
cytokines,
chemokines,
proteases,
bioactive
lipids,
inhibitory
molecules,
extracellular
vesicles,
metabolites,
lipids
other
factors,
able
to
promote
chronic
inflammation
tissue
dysfunction.
SnCs
up‐regulate
anti‐apoptotic
pathways
(SCAPs)
prevent
them
from
dying
despite
accumulation
damage
DNA
organelles.
These
SCAPs
altered
represent
targets
development
senotherapeutic
drugs
induce
selective
death
SnCs,
specifically
termed
senolytics
or
suppress
markers
senescence,
particular
SASP,
senomorphics.
Here,
we
review
current
senomorphics
treatment
age‐related
disorders
extension
healthy
longevity.
In
addition,
challenges
documenting
senolytic
senomorphic
activity
pre‐clinical
models
clinical
application
senotherapeutics
be
discussed.
EMBO Molecular Medicine,
Год журнала:
2019,
Номер
11(12)
Опубликована: Ноя. 19, 2019
Organismal
ageing
is
a
complex
process
driving
progressive
impairment
of
functionality
and
regenerative
potential
tissues.
Cellular
senescence
state
stable
cell
cycle
arrest
occurring
in
response
to
damage
stress
considered
hallmark
ageing.
Senescent
cells
accumulate
multiple
organs
during
ageing,
contribute
tissue
dysfunction
give
rise
pathological
manifestations.
Senescence
therefore
defining
feature
variety
human
age-related
disorders,
including
cancer,
targeted
elimination
these
has
recently
emerged
as
promising
therapeutic
approach
ameliorate
promote
repair
regeneration.
In
addition,
vivo
identification
senescent
significant
for
early
diagnosis
pathologies.
Here,
we
review
existing
senolytics,
small
molecules
drug
delivery
tools
used
preclinical
strategies
involving
cellular
senescence,
well
probes
trace
cells.
We
also
the
clinical
research
landscape
discuss
how
identifying
targeting
might
positively
affect
processes.
BMB Reports,
Год журнала:
2019,
Номер
52(1), С. 47 - 55
Опубликована: Янв. 31, 2019
Cellular
senescence
(CS)
is
one
of
hallmarks
aging
and
accumulation
senescent
cells
(SCs)
with
age
contributes
to
tissue
or
organismal
aging,
as
well
the
pathophysiologies
diverse
age-related
diseases
(ARDs).
Genetic
ablation
SCs
in
tissues
lengthened
health
span
reduced
risk
pathologies
a
mouse
model,
suggesting
direct
link
between
SCs,
longevity,
ARDs.
Therefore,
senotherapeutics,
medicines
targeting
might
be
an
emerging
strategy
for
extension
span,
prevention
treatment
Senotherapeutics
are
classified
senolytics
which
kills
selectively;
senomorphics
modulate
functions
morphology
those
young
cells,
delays
progression
tissues;
immune-system
mediators
clearance
SCs.
Some
have
been
proven
markedly
prevent
treat
ARDs
animal
models.
This
review
will
present
current
status
development
relation
itself
Finally,
future
directions
opportunities
senotherapeutics
use
discussed.
knowledge
provide
information
that
can
used
develop
novel
[BMB
Reports
2019;
52(1):
47-55].
