bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 4, 2023
ABSTRACT
Tight
junctions
are
a
barrier-forming
cell-cell
adhesion
complex
and
have
been
proposed
to
regulate
cell
proliferation.
However,
the
underlying
mechanisms
not
well
understood.
Here,
we
used
cells
deficient
in
junction
scaffold
ZO-1
alone
or
together
with
its
paralog
ZO-2,
which
disrupts
junctional
barrier.
We
found
that
knockout
increased
proliferation,
loss
of
density-dependent
proliferation
control,
promoted
death.
These
phenotypes
were
enhanced
by
double
ZO-1/ZO-2
knockout.
Increased
was
dependent
on
YAP
ZONAB,
two
transcriptional
regulators.
stimulated
nuclear
translocation
activity
without
changes
Hippo-dependent
phosphorylation.
Knockout
TANK-binding
Kinase
1
(TBK1)
activation
expression
RhoA
activator
GEF-H1.
Knockdown
ZO-3,
another
interacting
ZO1,
sufficient
induce
GEF-H1
activity.
GEF-H1,
TBK1,
mechanotransduction
at
focal
adhesions
required
for
YAP/TEAD
ZO-1-deficient
cells.
Thus,
controls
Hippo-independent
activating
GEF-H1-
TBK1-regulated
mechanosensitive
signalling
network.
Journal of Hepatocellular Carcinoma,
Journal Year:
2024,
Volume and Issue:
Volume 11, P. 1801 - 1821
Published: Sept. 1, 2024
Hepatobiliary
and
pancreatic
diseases
are
becoming
increasingly
common
worldwide
associated
cancers
prone
to
recurrence
metastasis.
For
a
more
accurate
treatment,
new
therapeutic
strategies
urgently
needed.
The
claudins
(CLDN)
family
comprises
class
of
membrane
proteins
that
the
main
components
tight
junctions,
essential
for
forming
intercellular
barriers
maintaining
cellular
polarity.
In
mammals,
claudin
contains
at
least
27
transmembrane
plays
major
role
in
mediating
cell
adhesion
paracellular
permeability.
Multiple
altered
various
cancers,
including
gastric
cancer
(GC),
esophageal
(EC),
hepatocellular
carcinoma
(HCC),
(PC),
colorectal
(CRC)
breast
(BC).
An
increasing
number
studies
have
shown
closely
with
occurrence
development
hepatobiliary
diseases.
Interestingly,
exhibit
different
effects
on
progression
tumor
tissues,
suppression
promotion.
addition,
currently
being
studied
as
potential
diagnostic
targets,
claudin-3,
claudin-4,
claudin-18.2,
etc.
this
article,
functional
phenotype,
molecular
mechanism,
targeted
application
reviewed,
an
emphasis
claudin-1,
claudin-7
current
situation
future
prospects
proposed.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 21, 2024
Abstract
To
preserve
barrier
function,
cell-cell
junctions
must
dynamically
remodel
during
cell
shape
changes.
We
have
previously
described
a
rapid
tight
junction
repair
pathway
characterized
by
local,
transient
activation
of
RhoA,
termed
‘Rho
flares,’
which
leaks
in
via
promoting
local
actomyosin-mediated
remodeling.
In
this
pathway,
elongation
is
mechanical
trigger
that
initiates
RhoA
through
an
influx
intracellular
calcium
and
recruitment
p115RhoGEF.
However,
mechanisms
tune
the
level
Myosin
II
contractility
process
remain
uncharacterized.
Here,
we
show
scaffolding
protein
Anillin
localizes
to
Rho
flares
regulates
activity
actomyosin
contraction
at
flares.
Knocking
down
results
with
increased
intensity
but
shorter
duration.
These
changes
active
dynamics
weaken
downstream
F-actin
accumulation
site
flares,
resulting
decreased
contraction.
Consequently,
breaks
are
not
reinforced
following
Anillin-driven
regulation
necessary
for
successfully
repairing
protecting
from
repeated
damage.
Together,
these
uncover
novel
regulatory
role
function
maintenance.
Significance
Statement
Barrier
critical
epithelial
tissues.
Epithelial
cells
maintain
junctions,
be
remodeled
allow
cell-
tissue-scale
How
maintained
as
change
remains
unclear.
The
required
generating
effective
reinforce
damaged
junctions;
lack
reinforcement
leads
leaks.
findings
highlight
remodeling
suggest
Anillin’s
ability
duration
affects
contractile
output.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 4, 2023
ABSTRACT
Tight
junctions
are
a
barrier-forming
cell-cell
adhesion
complex
and
have
been
proposed
to
regulate
cell
proliferation.
However,
the
underlying
mechanisms
not
well
understood.
Here,
we
used
cells
deficient
in
junction
scaffold
ZO-1
alone
or
together
with
its
paralog
ZO-2,
which
disrupts
junctional
barrier.
We
found
that
knockout
increased
proliferation,
loss
of
density-dependent
proliferation
control,
promoted
death.
These
phenotypes
were
enhanced
by
double
ZO-1/ZO-2
knockout.
Increased
was
dependent
on
YAP
ZONAB,
two
transcriptional
regulators.
stimulated
nuclear
translocation
activity
without
changes
Hippo-dependent
phosphorylation.
Knockout
TANK-binding
Kinase
1
(TBK1)
activation
expression
RhoA
activator
GEF-H1.
Knockdown
ZO-3,
another
interacting
ZO1,
sufficient
induce
GEF-H1
activity.
GEF-H1,
TBK1,
mechanotransduction
at
focal
adhesions
required
for
YAP/TEAD
ZO-1-deficient
cells.
Thus,
controls
Hippo-independent
activating
GEF-H1-
TBK1-regulated
mechanosensitive
signalling
network.
