Cancers,
Год журнала:
2022,
Номер
14(15), С. 3786 - 3786
Опубликована: Авг. 3, 2022
Phosphatase
and
Tensin
Homolog
deleted
on
Chromosome
10
(PTEN)
is
one
of
the
critical
tumor
suppressor
genes
main
negative
regulator
PI3K
pathway.
PTEN
frequently
found
to
be
inactivated,
either
partially
or
fully,
in
various
malignancies.
The
PI3K/AKT
pathway
considered
signaling
cues
that
drives
proliferation
cells.
Perhaps
it
not
surprising,
then,
this
hyperactivated
highly
proliferative
tumors.
Importantly,
also
coordinates
epithelial–mesenchymal
transition
(EMT),
which
pivotal
for
initiation
metastases
hence
regarded
as
an
attractive
target
treatment
metastatic
cancer.
It
was
shown
suppresses
EMT,
although
exact
mechanism
effect
still
fully
understood.
This
review
attempt
systematize
published
information
role
development
malignant
tumors,
with
a
focus
regulation
EMT.
Cancer
ranks
as
the
second
leading
cause
of
death
worldwide,
causing
a
large
social
and
economic
burden.
However,
most
anti-cancer
treatments
face
problems
tumor
recurrence
metastasis.
Therefore,
finding
an
effective
cure
for
cancer
needs
to
be
solved
urgently.
Recently,
discovery
stem
cells
(CSCs)
provides
new
orientation
research
therapy.
CSCs
share
main
characteristics
with
are
able
generate
entire
tumor.
Besides,
usually
escape
from
current
therapies,
which
is
partly
responsible
poor
prognosis.
microRNAs
(miRNAs)
belong
small
noncoding
RNA
regulate
gene
post-transcriptional
expression.
The
dysregulation
miRNAs
leads
plenty
diseases,
including
cancer.
aberrant
miRNA
expression
in
enhances
stemness
maintenance.
In
this
review,
we
summarize
role
on
eight
common
cancers,
hoping
bridge
clinical
applications.
We
found
that
can
act
promoter
or
suppressor.
cell
contributes
metastasis
therapeutic
resistance
via
formation
feedback
loops
constitutive
activation
carcinogenic
signaling
pathways.
More
importantly,
some
may
potential
targets
diagnosis,
prognosis,
treatments.
Journal of Cancer,
Год журнала:
2020,
Номер
12(1), С. 76 - 88
Опубликована: Ноя. 6, 2020
Background:
Triple-negative
breast
cancer
(TNBC)
is
a
great
threat
to
global
women's
health
due
its
high
metastatic
potential.
Epithelial-to-mesenchymal
transition
(EMT)
considered
as
key
event
in
the
process
of
metastasis.
So
pharmacological
targeting
EMT
might
be
promising
strategy
improving
therapeutic
efficacy
TNBC.
Here,
we
investigated
effect
shikonin
exerting
on
and
consequently
metastasis
TNBC
cells
underlying
mechanism.
Methods:
The
invasive
migratory
capacities
MDA-MB-231
BT549
were
tested
using
transwell
invasion
wound
healing
assay.
MiR-17-5p
expression
was
examined
by
qRT-PCR.
targeted
genes
predicted
with
different
bioinformatic
algorithms
from
four
databases
(TargetScan,
miRanda,
PITA
picTar)
further
screened
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
pathway
enrichment
analysis.
differential
expressions
their
correlations
miR-17-5p
identified
patients
based
Cancer
Genome
Atlas
(TCGA)
database.
interaction
between
phosphatase
tensin
homolog
deleted
chromosome
ten
(PTEN)
analyzed
luciferase
reporter
overexpression
vector
small
interfering
RNA
constructed
investigate
role
PTEN
played
regulation.
markers,
protein
kinase
B
(Akt)
phospho-Akt
(p-Akt)
evaluated
western
blot.
Results:
Shikonin
suppressed
migration
meanwhile
corresponding
alterations
biomarkers
observed
treated
cells.
inhibited
miR-17-5p,
which
upregulated
cancer.
3'-untranslated
region
(3'-UTR)
found
direct
binding
target
assays.
functioned
suppressor
both
Moreover,
Akt
p-Akt
(Ser473)
involved
inhibition
cell
migration,
shikonin.
Conclusions:
inhibits
suppressing
via
miR-17-5p/PTEN/Akt
pathway.
This
suggests
agent
counteract
patients.
Cell Death and Disease,
Год журнала:
2021,
Номер
12(6)
Опубликована: Май 18, 2021
Notch
receptors
(Notch1-4)
play
critical
roles
in
tumorigenesis
and
metastasis
of
malignant
tumors,
including
breast
cancer.
Although
abnormal
activation
is
related
to
various
the
importance
single
their
mechanism
distinct
cancer
subtypes
are
still
unclear.
Previous
studies
by
our
group
demonstrated
that
Notch3
may
inhibit
emergence
progression
PTEN
a
potent
tumor
suppressor,
its
loss
function
sufficient
promote
occurrence
tumors.
Intriguingly,
numerous
have
revealed
Notch1
involved
regulation
through
binding
CBF-1,
transcription
factor,
promoter.
In
this
study,
we
found
levels
correlated
with
luminal
phenotype
cell
lines.
Furthermore,
transactivated
CSL-binding
elements
promoter
and,
at
least
part,
inhibiting
downstream
AKT-mTOR
pathway.
Notably,
knockdown
downregulated
promoted
proliferation
tumorigenesis.
contrast,
overexpression
intracellular
domain
upregulated
inhibited
vitro
vivo.
Moreover,
inhibition
or
partially
reversed
promotion
induced
alterations.
general,
expression
positively
elevated
PTEN,
ER,
lower
Ki-67
index,
incidence
node
status
predicted
better
recurrence-free
survival
patients.
Therefore,
findings
demonstrate
inhibits
suppresses
transactivating
expression.
Cancers,
Год журнала:
2022,
Номер
14(15), С. 3786 - 3786
Опубликована: Авг. 3, 2022
Phosphatase
and
Tensin
Homolog
deleted
on
Chromosome
10
(PTEN)
is
one
of
the
critical
tumor
suppressor
genes
main
negative
regulator
PI3K
pathway.
PTEN
frequently
found
to
be
inactivated,
either
partially
or
fully,
in
various
malignancies.
The
PI3K/AKT
pathway
considered
signaling
cues
that
drives
proliferation
cells.
Perhaps
it
not
surprising,
then,
this
hyperactivated
highly
proliferative
tumors.
Importantly,
also
coordinates
epithelial–mesenchymal
transition
(EMT),
which
pivotal
for
initiation
metastases
hence
regarded
as
an
attractive
target
treatment
metastatic
cancer.
It
was
shown
suppresses
EMT,
although
exact
mechanism
effect
still
fully
understood.
This
review
attempt
systematize
published
information
role
development
malignant
tumors,
with
a
focus
regulation
EMT.
