Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Апрель 11, 2025
Epithelial-mesenchymal
transition
(EMT)
is
a
process
in
which
epithelial
cells,
defined
by
apical-basal
polarity
and
tight
intercellular
junctions,
acquire
migratory
invasive
properties
characteristic
of
mesenchymal
cells.
Under
normal
conditions,
EMT
directs
essential
morphogenetic
events
embryogenesis
supports
tissue
repair.
When
dysregulated,
contributes
to
pathological
processes
such
as
organ
fibrosis,
chronic
inflammation,
cancer
progression
metastasis.
Matrix
metalloproteinases
(MMPs)-a
family
zinc-dependent
proteases
that
degrade
structural
components
the
extracellular
matrix-sit
at
nexus
this
dismantling
basement
membranes,
activating
pro-EMT
signaling
pathways,
cleaving
adhesion
molecules.
normally
regulated,
MMPs
promote
balanced
ECM
turnover
support
cyclical
remodeling
necessary
for
proper
development,
wound
healing,
homeostasis.
abnormally
drive
excessive
turnover,
thereby
promoting
EMT-related
pathologies,
including
tumor
fibrotic
disease.
This
review
provides
an
integrated
overview
molecular
mechanisms
both
initiate
sustain
under
physiological
disease
conditions.
It
discusses
how
can
potentiate
through
TGF-β
Wnt/β-catenin
signaling,
disrupt
cell-cell
junction
proteins,
action
hypoxia-inducible
factors
microenvironment.
these
pathologic
remodel
tissues
during
fuel
cell
invasion,
metastasis,
resistance
therapy.
Finally,
explores
emerging
therapeutic
strategies
selectively
target
EMT,
ranging
from
CRISPR/Cas-mediated
interventions
engineered
inhibitors
(TIMPs),
demonstrates
approaches
may
suppress
without
compromising
its
indispensable
roles
biology.
Язык: Английский
Tumor Dormancy and Reactivation: The Role of Heat Shock Proteins
Cells,
Год журнала:
2024,
Номер
13(13), С. 1087 - 1087
Опубликована: Июнь 23, 2024
Tumors
are
a
heterogeneous
group
of
cell
masses
originating
in
various
organs
or
tissues.
The
cellular
composition
the
tumor
mass
interacts
an
intricate
manner,
influenced
by
humoral,
genetic,
molecular,
and
microenvironment
cues
that
dictate
growth
suppression.
As
result,
tumors
undergo
period
dormant
state
before
their
clinically
discernible
stage,
which
surpasses
clinical
dormancy
threshold.
Moreover,
as
genetically
imprinted
strategy,
early-seeder
cells,
distinct
population
break
off
to
dock
nearby
extravasate
into
blood
vessels
secondary
tissues,
where
they
form
disseminated
solitary
cells
with
reversible
capacity.
Among
mechanisms
underlying
formation,
heat
shock
proteins
(HSPs)
might
play
one
most
important
roles
how
program
plays
out.
It
is
known
numerous
aberrant
processes,
such
malignant
transformation,
cancer
stemness,
invasion,
metastasis,
angiogenesis,
signaling
pathway
maintenance,
HSPs.
An
accumulating
body
knowledge
suggests
HSPs
may
be
involved
angiogenic
switch,
immune
editing,
extracellular
matrix
(ECM)
remodeling
cascades,
crucial
strategies
initiation
maintenance
program.
In
this
review,
we
highlight
biological
events
orchestrate
work
has
been
conducted
on
dynamics
mass,
well
reactivation.
Additionally,
propose
conceptual
framework
could
possibly
underlie
reactivation
metastatic
relapse.
Язык: Английский
Dissecting the Puzzling Roles of FAM46C: A Multifaceted Pan-Cancer Tumour Suppressor with Increasing Clinical Relevance
Cancers,
Год журнала:
2024,
Номер
16(9), С. 1706 - 1706
Опубликована: Апрель 27, 2024
FAM46C
is
a
well-established
tumour
suppressor
with
role
that
not
completely
defined
or
universally
accepted.
Although
expression
down-modulated
in
several
tumours,
significant
mutations
the
gene
are
only
found
multiple
myeloma
(MM).
Consequently,
its
activity
has
primarily
been
studied
MM
context.
However,
emerging
evidence
suggests
involved
also
other
cancer
types,
namely
colorectal,
prostate
and
gastric
squamous
cell
hepatocellular
carcinoma,
where
was
to
be
significantly
reduced
tumoural
versus
non-tumoural
tissues
shown
possess
anti-proliferative
properties.
Accordingly,
recently
proposed
function
as
pan-cancer
prognostic
marker,
bringing
under
spotlight
attracting
growing
interest
from
scientific
community
pathways
modulated
by
mechanistic
activity.
Here,
we
will
provide
first
comprehensive
review
regarding
covering
(1)
intracellular
regulated
FAM46C,
MAPK/ERK,
PI3K/AKT,
β-catenin
TGF-β/SMAD
pathways;
(2)
models
mode
of
action,
specifically
poly(A)
polymerase,
trafficking
modulator
inhibitor
centriole
duplication
models,
focusing
on
connections
interdependencies;
(3)
regulation
different
environments
interferons,
IL-4,
TLR
engagement
transcriptional
modulators;
and,
lastly,
(4)
how
levels
associate
increased/decreased
sensitivity
anticancer
agents,
such
bortezomib,
dexamethasone,
lenalidomide,
pomalidomide,
doxorubicin,
melphalan,
SK1-I,
docetaxel
norcantharidin.
Язык: Английский
Non-Muscle Myosin II A: Friend or Foe in Cancer?
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(17), С. 9435 - 9435
Опубликована: Авг. 30, 2024
Non-muscle
myosin
IIA
(NM
IIA)
is
a
motor
protein
that
belongs
to
the
II
family.
The
heavy
chain
9
(MYH9)
gene
encodes
of
NM
IIA.
hexamer
and
contains
three
pairs
peptides,
which
include
dimer
chains,
essential
light
regulatory
chains.
part
actomyosin
complex
generates
mechanical
force
tension
carry
out
cellular
functions,
including
adhesion,
cytokinesis,
migration,
maintenance
cell
shape
polarity.
These
functions
are
regulated
via
phosphorylation
at
different
amino
acid
residues.
Apart
from
physiological
also
linked
development
cancer
genetic
neurological
disorders.
MYH9
mutations
result
in
several
autosomal
dominant
disorders,
such
as
May-Hegglin
anomaly
(MHA)
Epstein
syndrome
(EPS).
Multiple
studies
have
reported
tumor
suppressor
melanoma
head
neck
squamous
carcinoma;
however,
indicate
critical
player
promoting
tumorigenesis,
chemoradiotherapy
resistance,
stemness.
ROCK-NM
pathway
regulates
movement
control
cytoskeletal
dynamics.
In
addition,
dysregulated
various
solid
tumors
leukemia.
Currently,
there
very
few
compounds
targeting
IIA,
most
these
still
being
studied
preclinical
models.
This
review
provides
comprehensive
evidence
highlighting
dual
role
multiple
types
summarizes
signaling
networks
involved
tumorigenesis.
Furthermore,
we
discuss
potential
therapeutic
target
with
focus
on
pathway.
Язык: Английский
Identification of fibronectin type III domain containing 3B as a potential prognostic and therapeutic target for pancreatic cancer: a preliminary analysis
European journal of medical research,
Год журнала:
2024,
Номер
29(1)
Опубликована: Апрель 5, 2024
Abstract
Background
Fibronectin
type
III
domain
containing
3B
(FNDC3B),
a
member
of
the
fibronectin
domain-containing
protein
family,
has
been
indicated
in
various
malignancies.
However,
precise
role
FNDC3B
progression
pancreatic
cancer
(PC)
still
remains
to
be
elucidated.
Methods
In
this
study,
we
integrated
data
from
National
Center
for
Biotechnology
Information,
Cancer
Genome
Atlas,
Genotype-Tissue
Expression
database,
and
Gene
Omnibus
datasets
analyze
expression
its
association
with
clinicopathological
parameters.
Subsequently,
Ontology
Kyoto
Encyclopedia
Genes
Genomes,
along
Set
Enrichment
Analysis
(GSEA),
single
sample
(ssGSEA)
estimate
analysis
were
recruited
delve
into
biological
function
immune
infiltration
based
on
expression.
Additionally,
prognostic
estimation
was
conducted
using
Cox
Kaplan–Meier
analysis.
nomogram
constructed
according
result
enhance
ability
FNDC3B.
Finally,
preliminary
PC
cells
explored.
Results
The
study
demonstrated
significantly
higher
tumor
tissues
compared
normal
tissues,
associated
GSEA
revealed
involvement
processes
signaling
pathways
related
integrin
pathway
cell
adhesion.
ssGSEA
positive
correlation
between
Th2
neutrophils,
while
showing
negative
plasmacytoid
dendritic
Th17
infiltration.
further
supported
that
high
patients
linked
shorter
overall
survival,
disease-specific
progression-free
interval.
although
univariate
significant
prognosis
patients,
did
not
hold
true
multivariate
our
findings
highlight
crucial
regulating
proliferation,
migration,
invasion
abilities
cells.
Conclusion
Despite
limitations,
underscored
potential
as
biomarker
pivotal
driving
PC,
particularly
orchestrating
responses.
Язык: Английский