Cell Death and Disease,
Journal Year:
2020,
Volume and Issue:
11(7)
Published: July 8, 2020
Abstract
The
balance
between
cell
death
and
survival
is
a
critical
parameter
in
the
regulation
of
cells
maintenance
homeostasis
vivo.
Three
major
mechanisms
for
have
been
identified
mammalian
cells:
apoptosis
(type
I),
autophagic
II),
necrosis
III).
These
three
suggested
to
engage
cross
talk
with
each
other.
Among
them,
autophagy
was
originally
characterized
as
mechanism
amino
acid
recycling
during
starvation.
Whether
functions
primarily
or
question
yet
be
answered.
Here,
we
present
comprehensive
review
death-related
events
that
take
place
their
underlying
cancer
autoimmune
disease
development.
Frontiers in Oncology,
Journal Year:
2022,
Volume and Issue:
12
Published: March 24, 2022
Cancer
is
a
severe
public
health
issue
that
leading
cause
of
mortality
globally.
It
also
an
impediment
to
improving
life
expectancy
worldwide.
Furthermore,
the
global
burden
cancer
incidence
and
death
continuously
growing.
Current
therapeutic
options
are
insufficient
for
patients,
tumor
complexity
heterogeneity
necessitate
customized
medicine
or
targeted
therapy.
critical
identify
potential
targets.
Aberrant
activation
PI3K/AKT/mTOR
pathway
has
significant
role
in
carcinogenesis.
This
review
summarized
oncogenic
PI3K/Akt/mTOR
alterations
various
hallmarks
associated
with
pathway,
such
as
cell
proliferation,
autophagy,
apoptosis,
angiogenesis,
epithelial-to-mesenchymal
transition
(EMT),
chemoresistance.
Importantly,
this
provided
recent
advances
inhibitor
research.
Overall,
in-depth
understanding
association
between
tumorigenesis
development
therapies
targeting
will
help
make
clinical
decisions.
Cells,
Journal Year:
2020,
Volume and Issue:
9(10), P. 2308 - 2308
Published: Oct. 16, 2020
Aberrant
metabolism
is
a
major
hallmark
of
cancer.
Abnormal
cancer
metabolism,
such
as
aerobic
glycolysis
and
increased
anabolic
pathways,
has
important
roles
in
tumorigenesis,
metastasis,
drug
resistance,
stem
cells.
Well-known
oncogenic
signaling
phosphoinositide
3-kinase
(PI3K)/AKT,
Myc,
Hippo
pathway,
mediate
metabolic
gene
expression
increase
enzyme
activities.
Vice
versa,
deregulated
pathways
contribute
to
defects
cellular
signal
transduction
which
turn
provide
energy,
building
blocks,
redox
potentials
for
unrestrained
cell
proliferation.
Studies
clinical
trials
are
being
performed
that
focus
on
the
inhibition
enzymes
by
small
molecules
or
dietary
interventions
(e.g.,
fasting,
calorie
restriction,
intermittent
fasting).
Similar
genetic
heterogeneity,
phenotypes
cancers
highly
heterogeneous.
This
heterogeneity
results
from
diverse
cues
tumor
microenvironment
mutations.
Hence,
overcoming
plasticity
an
goal
modern
therapeutics.
review
highlights
recent
findings
elucidates
interactions
between
pathways.
We
also
novel
rationales
designing
next-generation
drugs.
Frontiers in Cell and Developmental Biology,
Journal Year:
2021,
Volume and Issue:
8
Published: Jan. 12, 2021
Metabolic
reprogramming
has
been
widely
recognized
as
a
hallmark
of
malignancy.
The
uptake
and
metabolism
amino
acids
are
aberrantly
upregulated
in
many
cancers
that
display
addiction
to
particular
acids.
Amino
facilitate
the
survival
proliferation
cancer
cells
under
genotoxic,
oxidative,
nutritional
stress.
Thus,
targeting
acid
is
becoming
potential
therapeutic
strategy
for
patients.
In
this
review,
we
will
systematically
summarize
recent
progress
malignancy
discuss
their
interconnection
with
mammalian
target
rapamycin
complex
1
(mTORC1)
signaling,
epigenetic
modification,
tumor
growth
immunity,
ferroptosis.
Finally,
highlight
applications.
Nature Cell Biology,
Journal Year:
2021,
Volume and Issue:
23(12), P. 1240 - 1254
Published: Dec. 1, 2021
Abstract
Extracellular
vesicles
and
exomere
nanoparticles
are
under
intense
investigation
as
sources
of
clinically
relevant
cargo.
Here
we
report
the
discovery
a
distinct
extracellular
nanoparticle,
termed
supermere.
Supermeres
morphologically
from
exomeres
display
markedly
greater
uptake
in
vivo
compared
with
small
exomeres.
The
protein
RNA
composition
supermeres
differs
highly
enriched
cargo
involved
multiple
cancers
(glycolytic
enzymes,
TGFBI,
miR-1246,
MET,
GPC1
AGO2),
Alzheimer’s
disease
(APP)
cardiovascular
(ACE2,
ACE
PCSK9).
majority
is
associated
rather
than
Cancer-derived
increase
lactate
secretion,
transfer
cetuximab
resistance
decrease
hepatic
lipids
glycogen
vivo.
This
study
identifies
functional
nanoparticle
replete
potential
circulating
biomarkers
therapeutic
targets
for
host
human
diseases.
Cancers,
Journal Year:
2021,
Volume and Issue:
13(16), P. 3949 - 3949
Published: Aug. 5, 2021
The
PI3K/AKT
pathway
is
one
of
the
most
frequently
over-activated
intracellular
pathways
in
several
human
cancers.
This
pathway,
acting
on
different
downstream
target
proteins,
contributes
to
carcinogenesis,
proliferation,
invasion,
and
metastasis
tumour
cells.
A
multi-level
impairment,
involving
mutation
genetic
alteration,
aberrant
regulation
miRNAs
sequences,
abnormal
phosphorylation
cascade
factors,
has
been
found
multiple
cancer
types.
deregulation
this
counteracts
common
therapeutic
strategies
multidrug
resistance.
In
review,
we
underline
involvement
patho-physiological
cell
survival
mechanisms,
emphasizing
its
key
role
development
drug
We
also
provide
an
overview
potential
inhibition
currently
available.
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2022,
Volume and Issue:
41(1)
Published: Jan. 8, 2022
Abstract
Background
Acquired
resistance
of
5-fluorouracil
(5-FU)
remains
a
clinical
challenge
in
colorectal
cancer
(CRC),
and
efforts
to
develop
targeted
agents
reduce
have
not
yielded
success.
Metabolic
reprogramming
is
key
hallmark
confers
several
tumor
phenotypes
including
chemoresistance.
Glucose
metabolic
events
5-FU
CRC
has
been
evaluated,
whether
abnormal
glucose
metabolism
could
impart
also
poorly
defined.
Methods
Three
separate
acquired
cell
line
models
were
generated,
was
assessed
by
measuring
lactate
utilization,
RNA
protein
expressions
metabolism-related
enzymes
changes
intermediate
metabolites
metabolite
pool.
The
levels
hypoxia
inducible
factor
1α
(HIF-1α)
primary
tumors
circulating
cells
patients
detected
immunohistochemistry
immunofluorescence.
Stable
HIF1A
knockdown
established
with
lentiviral
system.
influence
both
gene
pharmacological
inhibition
on
evaluated
vivo
vitro.
Results
abnormality
5-FU-resistant
described
detail.
enhanced
glycolysis
pentose
phosphate
pathway
associated
increased
HIF-1α
expression.
HIF-1α-induced
imparted
CRC.
showed
expression
lines
specimens,
failure
fluorouracil
analog-based
chemotherapy
poor
survival.
Upregulation
occurred
through
non-oxygen-dependent
mechanisms
reactive
oxygen
species-mediated
activation
PI3K/Akt
signaling
aberrant
β-catenin
the
nucleus.
Both
knock-down
restored
sensitivity
5-FU.
Conclusions
potential
biomarker
for
CRC,
targeting
HIF-1a
combination
may
represent
an
effective
therapeutic
strategy
Frontiers in Cell and Developmental Biology,
Journal Year:
2021,
Volume and Issue:
9
Published: July 1, 2021
The
mechanistic
target
of
rapamycin
(mTOR),
master
regulator
cellular
metabolism,
exists
in
two
distinct
complexes:
mTOR
complex
1
and
2
(mTORC1
2).
MTORC1
is
a
switch
for
most
energetically
onerous
processes
the
cell,
driving
cell
growth
building
biomass
instances
nutrient
sufficiency,
conversely,
allowing
autophagic
recycling
components
upon
limitation.
means
by
which
kinase
blocks
autophagy
include
direct
inhibition
early
steps
process,
control
lysosomal
degradative
capacity
inhibiting
transactivation
genes
encoding
structural,
regulatory,
catalytic
factors.
Upon
mTOR,
results
reactivation
mTORC1;
thus,
lies
both
downstream
upstream
mTOR.
functional
relationship
between
pathway
involves
regulatory
loops
that
are
significantly
deciphered
at
level,
but
incompletely
understood
physiological
level.
Nevertheless,
genetic
evidence
stemming
from
use
engineered
strains
mice
has
provided
significant
insight
into
overlapping
complementary
metabolic
effects
activity
exert
during
fasting
overload.
