Targeting
the
cross-talk
between
tumor-initiating
cells
(TICs)
and
niche
microenvironment
is
an
attractive
avenue
for
cancer
therapy.
We
show
here,
using
a
mouse
model
of
squamous
cell
carcinoma,
that
TICs
play
crucial
role
in
creating
required
tumor
progression
drug
resistance.
Antioxidant
activity
TICs,
mediated
by
transcription
factor
NRF2,
facilitates
release
nuclear
cytokine,
interleukin-33
(IL-33).
This
cytokine
promotes
differentiation
macrophages
express
high-affinity
immunoglobulin
E
receptor
FcεRIα
are
close
proximity
to
TICs.
In
turn,
these
IL-33-responding
International Journal of Molecular Sciences,
Год журнала:
2019,
Номер
20(11), С. 2767 - 2767
Опубликована: Июнь 5, 2019
Transforming
growth
factor
β
(TGF-β)
is
a
secreted
cytokine
that
regulates
cell
proliferation,
migration,
and
the
differentiation
of
plethora
different
types.
Consistent
with
these
findings,
TGF-β
plays
key
role
in
controlling
embryogenic
development,
inflammation,
tissue
repair,
as
well
maintaining
adult
homeostasis.
elicits
broad
range
context-dependent
cellular
responses,
consequently,
alterations
signaling
have
been
implicated
many
diseases,
including
cancer.
During
early
stages
tumorigenesis,
acts
tumor
suppressor
by
inducing
cytostasis
apoptosis
normal
premalignant
cells.
However,
at
later
stages,
when
cancer
cells
acquired
oncogenic
mutations
and/or
lost
gene
function,
are
resistant
to
TGF-β-induced
arrest,
functions
promotor
stimulating
undergo
so-called
epithelial-mesenchymal
transition
(EMT).
The
latter
leads
metastasis
chemotherapy
resistance.
further
supports
progression
activating
angiogenesis
cancer-associated
fibroblasts
enabling
evade
inhibitory
immune
responses.
In
this
review,
we
will
consider
cycle
apoptosis,
EMT
metastasis.
particular,
highlight
recent
insights
into
multistep
dynamically
controlled
process
miRNAs
long
noncoding
RNAs
process.
Finally,
discuss
how
new
mechanistic
might
be
exploited
develop
novel
therapeutic
interventions.
Cell,
Год журнала:
2020,
Номер
182(2), С. 497 - 514.e22
Опубликована: Июнь 23, 2020
To
define
the
cellular
composition
and
architecture
of
cutaneous
squamous
cell
carcinoma
(cSCC),
we
combined
single-cell
RNA
sequencing
with
spatial
transcriptomics
multiplexed
ion
beam
imaging
from
a
series
human
cSCCs
matched
normal
skin.
cSCC
exhibited
four
tumor
subpopulations,
three
recapitulating
epidermal
states,
tumor-specific
keratinocyte
(TSK)
population
unique
to
cancer,
which
localized
fibrovascular
niche.
Integration
data
mapped
ligand-receptor
networks
specific
types,
revealing
TSK
cells
as
hub
for
intercellular
communication.
Multiple
features
potential
immunosuppression
were
observed,
including
T
regulatory
(Treg)
co-localization
CD8
in
compartmentalized
stroma.
Finally,
characterization
xenografts
vivo
CRISPR
screens
identified
essential
roles
subpopulation-enriched
gene
tumorigenesis.
These
stromal
niches
where
they
interact,
communicating
that
engage
cancer.
Transforming
growth
factor
β
(TGF-β)
has
long
been
identified
with
its
intensive
involvement
in
early
embryonic
development
and
organogenesis,
immune
supervision,
tissue
repair,
adult
homeostasis.
The
role
of
TGF-β
fibrosis
cancer
is
complex
sometimes
even
contradictory,
exhibiting
either
inhibitory
or
promoting
effects
depending
on
the
stage
disease.
Under
pathological
conditions,
overexpressed
causes
epithelial-mesenchymal
transition
(EMT),
extracellular
matrix
(ECM)
deposition,
cancer-associated
fibroblast
(CAF)
formation,
which
leads
to
fibrotic
disease,
cancer.
Given
critical
downstream
molecules
progression
cancers,
therapeutics
targeting
signaling
appears
be
a
promising
strategy.
However,
due
potential
systemic
cytotoxicity,
lagged.
In
this
review,
we
summarized
biological
process
TGF-β,
dual
tumorigenesis,
clinical
application
TGF-β-targeting
therapies.
Biomolecules,
Год журнала:
2020,
Номер
10(3), С. 487 - 487
Опубликована: Март 23, 2020
Transforming
growth
factor-β
(TGF-β)
represents
an
evolutionarily
conserved
family
of
secreted
polypeptide
factors
that
regulate
many
aspects
physiological
embryogenesis
and
adult
tissue
homeostasis.
The
TGF-β
members
are
also
involved
in
pathophysiological
mechanisms
underlie
diseases.
Although
the
comprises
factors,
which
exhibit
cell
type-specific
developmental
stage-dependent
biological
actions,
they
all
signal
via
signaling
pathways.
controlled
at
extracellular
level,
where
ligand
secretion,
deposition
to
matrix
activation
prior
play
important
roles.
At
plasma
membrane
TGF-βs
associate
with
receptor
kinases
mediate
phosphorylation-dependent
downstream
mediators,
mainly
SMAD
proteins,
oligomerization-dependent
ubiquitin
ligases
intracellular
protein
kinases.
interplay
between
SMADs
other
proteins
regulatory
signals
control
expression
target
genes,
RNA
processing
multiple
levels,
mRNA
translation
nuclear
or
cytoplasmic
regulation.
This
article
emphasizes
importance
biochemical
executing
functions
by
prototype
member
family,
TGF-β.
