Cancers,
Год журнала:
2023,
Номер
15(20), С. 4956 - 4956
Опубликована: Окт. 12, 2023
Yes-associated
Protein
(YAP)
and
its
paralog
Transcriptional
Coactivator
with
PDZ-binding
Motif
(TAZ)
are
major
regulators
of
gene
transcription/expression,
primarily
controlled
by
the
Hippo
pathway
cytoskeleton.
Integrating
an
array
chemical
mechanical
signals,
they
impact
growth,
differentiation,
regeneration.
Accordingly,
also
play
key
roles
in
tumorigenesis
metastasis
formation.
Their
activity
is
regulated
their
localization,
that
is,
pathway-
and/or
cytoskeleton-controlled
cytosolic
or
nuclear
sequestration.
While
many
details
such
prevailing
retention
models
have
been
elucidated,
much
less
known
about
actual
traffic:
import
export.
Although
size
not
far
from
cutoff
for
passive
diffusion
through
pore
complex
(NPC),
do
contain
any
classic
localization
(NLS)
export
signal
(NES),
evidence
has
accumulating
shuttling
involves
mediated
thus
regulatable/targetable
processes.
The
aim
this
review
to
summarize
emerging
information/concepts
nucleocytoplasmic
shuttling,
encompassing
relevant
structural
requirements
(NLS,
NES),
transport
receptors
(NTRs,
karyophererins),
NPC
components,
along
potential
mechanisms
regulation.
dissecting
vs.
often
challenging,
picture
suggests
YAP/TAZ
shuttles
across
via
multiple,
non-exclusive,
mechanisms,
constituting
a
novel
intriguing
facet
biology.
Pharmacological Research,
Год журнала:
2024,
Номер
203, С. 107167 - 107167
Опубликована: Апрель 9, 2024
Cancer
has
become
a
burgeoning
global
healthcare
concern
marked
by
its
exponential
growth
and
significant
economic
ramifications.
Though
advancements
in
the
treatment
modalities
have
increased
overall
survival
quality
of
life,
there
are
no
definite
treatments
for
advanced
stages
this
malady.
Hence,
understanding
diseases
etiologies
underlying
molecular
complexities,
will
usher
development
innovative
therapeutics.
Recently,
YAP/TAZ
transcriptional
regulation
been
immense
interest
due
to
their
role
development,
tissue
homeostasis
oncogenic
transformations.
axis
functions
as
coactivators
within
Hippo
signaling
cascade,
exerting
pivotal
influence
on
processes
such
proliferation,
regeneration,
renewal.
In
cancer,
YAP
is
overexpressed
multiple
tumor
types
associated
with
cancer
stem
cell
attributes,
chemoresistance,
metastasis.
Activation
mirrors
cellular
"social"
behavior,
encompassing
factors
adhesion
mechanical
signals
transmitted
from
structure
surrounding
extracellular
matrix.
Therefore,
it
presents
vulnerability
clogs
tumors
that
could
provide
wide
window
therapeutic
effectiveness.
Natural
compounds
utilized
extensively
successful
interventions
management
diverse
chronic
illnesses,
including
cancer.
Owing
capacity
genes
pathways,
natural
exhibit
potential
either
adjuvant
therapy
or
combination
conventional
options.
review,
we
delineate
nexus
axis,
present
an
alternate
strategy
target
Journal of Cellular and Molecular Medicine,
Год журнала:
2024,
Номер
28(8)
Опубликована: Апрель 1, 2024
Abstract
The
Hippo
signalling
pathway,
a
highly
conserved
cassette,
regulates
organ
size
by
controlling
cell
growth,
apoptosis
and
stem
self‐renewal.
tumourigenic
potential
of
this
pathway
is
largely
attributed
to
the
activity
YAP/TAZ,
which
activate
TEAD1‐4
transcription
factors,
leading
expression
genes
involved
in
proliferation
suppression
death.
Aberrant
regulation
YAP/TAZ‐TEAD
axis
commonly
observed
malignant
pleural
mesothelioma
(MPM),
an
insidious
neoplasm
tissue
that
lines
chest
cavity
covers
lungs
with
poor
prognosis.
Given
limited
effectiveness
current
treatments,
targeting
cascade
has
emerged
as
promising
therapeutic
strategy
MPM.
Several
inhibitors
are
presently
undergoing
clinical
development,
goal
advancing
them
use
near
future.
International Journal of Oncology,
Год журнала:
2024,
Номер
65(2)
Опубликована: Июнь 14, 2024
Genes
encoding
subunits
of
SWI/SNF
(BAF)
chromatin‑remodeling
complexes
are
recurrently
mutated
in
a
broad
array
tumor
types,
and
among
the
subunits,
ARID1A
is
most
frequent
target
with
mutations.
In
present
study,
it
was
reported
that
inhibits
epithelial‑mesenchymal
transition
(EMT)
stemness
ovarian
cancer
cells,
accompanied
by
reduced
cell
viability,
migration
colony
formation,
suggesting
acts
as
suppressor
cancer.
Mechanistically,
exerts
its
inhibitory
effects
on
cells
activating
Hippo
signaling
pathway.
Conversely,
overexpression
gain‑of‑function
transcriptional
co‑activator
PDZ‑binding
motif
(TAZ)
mutant
(TAZ‑Ser89)
effectively
reverses
induced
ARID1A.
addition,
activation
apparently
upregulates
protein
expression,
whereas
ectopic
expression
TAZ‑Ser89
results
markedly
decreased
levels,
indicating
feedback
ARID1A‑TAZ
regulating
EMT
stemness.
Thus,
study
uncovered
role
through
Hippo/TAZ
pathway
modulating
providing
evidence
TAZ
inhibitors
could
prevent
initiation
metastasis
cases
where
lost
or
mutated.
Cancers,
Год журнала:
2023,
Номер
15(20), С. 4956 - 4956
Опубликована: Окт. 12, 2023
Yes-associated
Protein
(YAP)
and
its
paralog
Transcriptional
Coactivator
with
PDZ-binding
Motif
(TAZ)
are
major
regulators
of
gene
transcription/expression,
primarily
controlled
by
the
Hippo
pathway
cytoskeleton.
Integrating
an
array
chemical
mechanical
signals,
they
impact
growth,
differentiation,
regeneration.
Accordingly,
also
play
key
roles
in
tumorigenesis
metastasis
formation.
Their
activity
is
regulated
their
localization,
that
is,
pathway-
and/or
cytoskeleton-controlled
cytosolic
or
nuclear
sequestration.
While
many
details
such
prevailing
retention
models
have
been
elucidated,
much
less
known
about
actual
traffic:
import
export.
Although
size
not
far
from
cutoff
for
passive
diffusion
through
pore
complex
(NPC),
do
contain
any
classic
localization
(NLS)
export
signal
(NES),
evidence
has
accumulating
shuttling
involves
mediated
thus
regulatable/targetable
processes.
The
aim
this
review
to
summarize
emerging
information/concepts
nucleocytoplasmic
shuttling,
encompassing
relevant
structural
requirements
(NLS,
NES),
transport
receptors
(NTRs,
karyophererins),
NPC
components,
along
potential
mechanisms
regulation.
dissecting
vs.
often
challenging,
picture
suggests
YAP/TAZ
shuttles
across
via
multiple,
non-exclusive,
mechanisms,
constituting
a
novel
intriguing
facet
biology.
