Signal Transduction and Targeted Therapy,
Journal Year:
2020,
Volume and Issue:
5(1)
Published: Dec. 26, 2020
Abstract
Hepatocyte
nuclear
factor
3γ
(HNF3γ)
is
a
hepatocyte
factor,
but
its
role
and
clinical
significance
in
hepatocellular
carcinoma
(HCC)
remain
unclear.
Herein,
we
report
that
HNF3γ
expression
downregulated
patient
HCC
inversely
correlated
with
malignancy
survival.
Moreover,
our
data
suggested
the
reduction
could
be
mediated
by
METTL14-dependent
m6A
methylation
of
mRNA.
was
increased
during
hepatic
differentiation
decreased
dedifferentiated
cells.
Interestingly,
delivery
promoted
not
only
cells
also
liver
CSCs,
which
led
to
suppression
growth.
Mechanistic
analysis
an
HNF3γ-centered
regulatory
network
includes
essential
differentiation-associated
transcription
factors
functional
molecules,
synergistically
facilitate
cell
differentiation.
More
importantly,
enforced
sensitized
sorafenib-induced
growth
inhibition
apoptosis
through
transactivation
OATP1B1
OATP1B3
expression,
are
major
membrane
transporters
for
sorafenib
uptake.
Clinical
investigation
showed
patient-derived
xenografts
high
exhibited
response
patients
levels
benefited
from
therapy.
Together,
these
results
suggest
plays
may
serve
as
therapeutic
target
predictor
benefit
patients.
Cancer Discovery,
Journal Year:
2022,
Volume and Issue:
12(1), P. 31 - 46
Published: Jan. 1, 2022
The
hallmarks
of
cancer
conceptualization
is
a
heuristic
tool
for
distilling
the
vast
complexity
phenotypes
and
genotypes
into
provisional
set
underlying
principles.
As
knowledge
mechanisms
has
progressed,
other
facets
disease
have
emerged
as
potential
refinements.
Herein,
prospect
raised
that
phenotypic
plasticity
disrupted
differentiation
discrete
hallmark
capability,
nonmutational
epigenetic
reprogramming
polymorphic
microbiomes
both
constitute
distinctive
enabling
characteristics
facilitate
acquisition
capabilities.
Additionally,
senescent
cells,
varying
origins,
may
be
added
to
roster
functionally
important
cell
types
in
tumor
microenvironment.
SIGNIFICANCE:
Cancer
daunting
breadth
scope
its
diversity,
spanning
genetics,
tissue
biology,
pathology,
response
therapy.
Ever
more
powerful
experimental
computational
tools
technologies
are
providing
an
avalanche
"big
data"
about
myriad
manifestations
diseases
encompasses.
integrative
concept
embodied
helping
distill
this
increasingly
logical
science,
new
dimensions
presented
perspective
add
value
endeavor,
fully
understand
development
malignant
progression,
apply
medicine.
Proceedings of the National Academy of Sciences,
Journal Year:
2019,
Volume and Issue:
116(18), P. 9020 - 9029
Published: April 17, 2019
Significance
The
exclusion
of
immune
cells
from
the
tumor
microenvironment
has
been
associated
with
poor
prognosis
in
majority
cancers.
We
report
that
when
considering
21
solid
cancer
types,
cell
is
widely
presence
a
stem
cell-like
phenotype
tumors
(“stemness”).
Stemness
positively
correlates
higher
intratumoral
heterogeneity,
possibly
by
protecting
antigenic
clones
elimination
system.
activation
stemness
program
appears
to
limit
antitumor
responses
via
cell-intrinsic
silencing
endogenous
retrovirus
expression,
repression
type
I
interferon
signaling,
and
up-regulation
immunosuppressive
checkpoints.
Our
work
suggests
targeting
will
promote
T
infiltration
render
more
responsive
control.
Theranostics,
Journal Year:
2020,
Volume and Issue:
11(3), P. 1016 - 1030
Published: Nov. 6, 2020
Macrophages
phagocytize
pathogens
to
initiate
innate
immunity
and
products
from
the
tumor
microenvironment
(TME)
mediate
immunity.
The
loss
of
tumor-associated
macrophage
(TAM)-mediated
immune
responses
results
in
suppression.
To
reverse
this
disorder,
regulatory
mechanism
TAMs
TME
needs
be
clarified.
Immune
molecules
(cytokines
chemokines)
have
been
widely
accepted
as
mutual
mediators
signal
transduction
past
few
decades.
Recently,
researchers
tried
seek
intrinsic
TAM
phenotypic
functional
changes
through
metabolic
connections.
Numerous
metabolites
derived
identified
that
induce
cell-cell
crosstalk
with
TAMs.
bulk
cells,
stromal
cells
produce
are
involved
regulation
Meanwhile,
some
regulate
biological
functions
well.
Here,
we
review
recent
reports
demonstrating
between
Science,
Journal Year:
2022,
Volume and Issue:
377(6611), P. 1180 - 1191
Published: Aug. 18, 2022
Drug
resistance
in
cancer
is
often
linked
to
changes
tumor
cell
state
or
lineage,
but
the
molecular
mechanisms
driving
this
plasticity
remain
unclear.
Using
murine
organoid
and
genetically
engineered
mouse
models,
we
investigated
causes
of
lineage
prostate
its
relationship
antiandrogen
resistance.
We
found
that
initiates
an
epithelial
population
defined
by
mixed
luminal-basal
phenotype
it
depends
on
increased
Janus
kinase
(JAK)
fibroblast
growth
factor
receptor
(FGFR)
activity.
Organoid
cultures
from
patients
with
castration-resistant
disease
harboring
mixed-lineage
cells
reproduce
dependency
observed
mice
up-regulating
luminal
gene
expression
upon
JAK
FGFR
inhibitor
treatment.
Single-cell
analysis
confirms
presence
JAK/STAT
(signal
transducer
activator
transcription)
signaling
a
subset
metastatic
disease,
implications
for
stratifying
clinical
trials.
