bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Дек. 14, 2022
SUMMARY
In
proliferating
neoplasms,
microenvironment-derived
selective
pressures
promote
tumor
heterogeneity
by
imparting
diverse
capacities
for
growth,
differentiation
and
invasion.
However,
what
makes
a
cell
respond
to
signaling
cues
differently
from
normal
is
not
well
understood.
the
Drosophila
ovarian
follicle
cells,
apicobasal-polarity
loss
induces
heterogenous
epithelial
multilayering.
When
exacerbated
oncogenic-Notch
expression,
this
multilayer
displays
an
increased
consistency
in
occurrence
of
morphologically
distinguishable
cells
adjacent
polar
cells.
Polar
release
Jak-STAT
ligand
Unpaired
(Upd),
response
which,
neighboring
polarity-deficient
exhibit
precursor-like
transcriptomic
state.
Using
single-cell
transcriptomics,
we
discovered
ectopic
activation
Snail-family
transcription
factor
Escargot
(Esg)
these
We
also
characterized
similar
relationship
between
Upd
Esg
during
early
follicular
development,
where
establishment
polarity
determines
follicle-cell
differentiation.
Overall,
our
results
indicate
that
epithelial-cell
acts
as
gatekeeper
against
microenvironmental
drive
heterogeneity.
Proteolysis
targeting
chimera
(PROTAC)
technology
has
become
a
powerful
strategy
in
drug
discovery,
especially
for
undruggable
targets/proteins.
A
typical
PROTAC
degrader
consists
of
three
components:
small
molecule
that
binds
to
target
protein,
an
E3
ligase
ligand
(consisting
and
its
recruiter),
chemical
linker
hooks
first
two
components
together.
In
the
past
20
years,
we
have
witnessed
advancement
multiple
degraders
into
clinical
trials
anticancer
therapies.
However,
one
major
challenges
is
only
very
limited
number
recruiters
are
currently
available
as
targeted
protein
degradation
(TPD),
although
human
genome
encodes
more
than
600
ligases.
Thus,
there
urgent
need
identify
additional
effective
TPD
applications.
this
review,
summarized
existing
RING-type
ubiquitin
their
act
ligands
application
discovery.
We
believe
review
could
serve
reference
future
development
efficient
cancer
discovery
development.
The Journal of Cell Biology,
Год журнала:
2023,
Номер
223(1)
Опубликована: Дек. 13, 2023
Cell
polarity,
which
consists
of
the
morphological,
structural,
and
functional
organization
cells
along
a
defined
axis,
is
feature
healthy
tissues.
In
contrast,
abnormal
polarity
hallmark
cancer
cells.
At
molecular
level,
key
evolutionarily
conserved
proteins
that
control
establishment
maintenance
in
various
contexts
are
frequently
altered
cancer,
but
relevance
these
alterations
oncogenic
processes
not
always
clear.
Here,
we
summarize
recent
findings,
shedding
new
light
on
involvement
players
development,
discuss
possibility
harnessing
cell
changes
to
better
predict,
diagnose,
cure
cancers.
Long
terminal
repeat
(LTR)
retrotransposons
belong
to
the
transposable
elements
(TEs),
autonomously
replicating
genetic
that
integrate
into
host's
genome.
Among
animals,
Drosophila
melanogaster
serves
as
an
important
model
organism
for
TE
research
and
contains
several
LTR
retrotransposons,
including
Ty1-copia
family,
which
is
evolutionarily
related
retroviruses
forms
virus-like
particles
(VLPs).
In
this
study,
we
use
cryo-focused
ion
beam
(FIB)
milling
lift-out
approaches
visualize
copia
VLPs
in
ovarian
cells
intact
egg
chambers,
resolving
situ
capsid
structure
7.7
Å
resolution
by
cryoelectron
tomography
(cryo-ET).
Although
cytoplasmic
vary
size,
nuclear
are
homogeneous
form
densely
packed
clusters,
supporting
a
import
acts
size
selector.
Analyzing
flies
deficient
TE-suppressing
PIWI-interacting
RNA
(piRNA)
pathway,
observe
copia's
translocation
nucleus
during
spermatogenesis.
Our
findings
provide
insights
replication
cycle
cellular
structural
biology
of
active
retrotransposon.
Quantitative
traits
are
often
complex
because
of
the
contribution
many
loci,
with
further
complexity
added
by
environmental
factors.
In
medical
research,
systems
genetics
is
a
powerful
approach
for
study
traits,
as
it
integrates
intermediate
phenotypes,
such
RNA,
protein,
and
metabolite
levels,
to
understand
molecular
physiological
phenotypes
linking
discrete
DNA
sequence
variation
clinical
traits.
The
primary
purpose
this
review
describe
some
resources
tools
in
humans
rodent
models,
so
that
researchers
areas
biology
medicine
can
make
use
data.
Cell Reports,
Год журнала:
2023,
Номер
42(2), С. 112061 - 112061
Опубликована: Янв. 28, 2023
In
proliferating
neoplasms,
microenvironment-derived
selective
pressures
promote
tumor
heterogeneity
by
imparting
diverse
capacities
for
growth,
differentiation,
and
invasion.
However,
what
makes
a
cell
respond
to
signaling
cues
differently
from
normal
is
not
well
understood.
the
Drosophila
ovarian
follicle
cells,
apicobasal-polarity
loss
induces
heterogeneous
epithelial
multilayering.
When
exacerbated
oncogenic-Notch
expression,
this
multilayer
displays
an
increased
consistency
in
occurrence
of
morphologically
distinguishable
cells
adjacent
polar
cells.
Polar
release
Jak/STAT
ligand
Unpaired
(Upd),
response
which
neighboring
polarity-deficient
exhibit
precursor-like
transcriptomic
state.
Among
several
regulons
active
these
we
could
detect
further
validate
expression
Snail
family
transcription
factor
Escargot
(Esg).
We
also
ascertain
similar
relationship
between
Upd
Esg
normally
developing
ovaries,
where
establishment
polarity
determines
early
follicular
differentiation.
Overall,
our
results
indicate
that
epithelial-cell
acts
as
gatekeeper
against
microenvironmental
drive
heterogeneity.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 22, 2024
Abstract
Long
terminal
repeat
(LTR)
retrotransposons
belong
to
the
transposable
elements
(TE),
autonomously
replicating
genetic
that
integrate
into
host’s
genome.
LTR
represent
a
major
component
of
genomes
across
tree
life;
some
derived
sequences
have
even
been
domesticated
by
host
perform
cellular
functions
in
essential
processes
such
as
development.
Among
animals,
Drosophila
melanogaster
serves
an
important
model
organism
for
TE
research,
harboring
several
retrotransposons,
including
Ty1-
copia
family,
which
is
evolutionarily
related
retroviruses
and
forms
virus-like
particles
(VLPs).
The
architectural
organization
VLPs
situ
has
remained
unknown.
In
this
study,
we
use
cryo-FIB
milling
lift-out
approaches
visualize
isolated
ovarian
cells
intact
egg
chambers
resolve
capsid
structure
7.7
Å
resolution
cryo-ET.
While
cytosolic
vary
size,
nuclear
are
homogenous
form
densely
packed
clusters,
supporting
import
acts
size
selector.
By
analyzing
flies
deficient
TE-suppressing
PIWI-piRNA
pathway,
observe
change
localization
from
during
spermatogenesis
testes.
Our
findings
provide
insights
structural
biology
active
retrotransposon
shed
light
on
replication
cycle
context
gametogenesis.
Epithelial
tissues
serve
as
critical
barriers
in
metazoan
organisms,
maintaining
structural
integrity
and
facilitating
essential
physiological
functions.
cell
polarity
regulates
mechanical
properties,
signaling,
transport,
ensuring
tissue
organization
homeostasis.
However,
the
barrier
function
is
challenged
by
turnover
during
development
maintenance.
To
preserve
while
removing
dying
or
unwanted
cells,
epithelial
employ
extrusion.
This
process
removes
both
dead
live
cells
from
layer,
typically
causing
detached
to
undergo
apoptosis.
Transformed
however,
often
resist
apoptosis,
leading
multilayered
structures
early
carcinogenesis.
Malignant
may
invade
neighboring
tissues.
Loss
of
can
lead
multilayer
formation,
extrusion,
invasion.
Recent
studies
indicate
that
formation
with
loss
involves
a
mixture
wild-type
mutant
apical
basal
accumulation.
The
directionality
accumulation
regulated
mutations
complex
genes.
phenomenon,
distinct
traditional
exhibits
similarities
endophytic
exophytic
growth
observed
human
tumors.
review
explores
regulation
implications
these
phenomena
for
biology
disease
pathology.
Tumor
growth
and
progression
involve
coordinated
regulation
by
internal,
microenvironmental,
systemic
signals
often
display
conspicuous
sexual
dimorphism.
The
mechanisms
governing
the
integration
coordination
of
these
signals,
along
with
their
sex-based
differences,
remain
largely
unknown.
Using
a
Drosophila
tumor
model
originating
from
nonreproductive
tissue,
we
show
that
female-biased
involves
multifaceted
communications
among
cells,
hemocytes,
neuroendocrine
insulin-producing
cells
(IPCs).
Notch-active
recruit
hemocytes
carrying
necrosis
factor–α
(TNF-α)
homolog
Eiger
to
microenvironment
(TME),
activating
c-Jun
N-terminal
kinase
(JNK)
pathway
in
instigating
sexually
dimorphic
up-regulation
cytokine
Unpaired
2
(Upd2).
Upd2,
turn,
exerts
distal
influence
modulating
release
insulin-like
peptide
(Dilp2)
IPCs.
Dilp2
then
activates
insulin
signaling
tumor,
thereby
fostering
sexual-dimorphic
growth.
Together,
findings
reveal
relay
mechanism
involving
TME
collectively
control
dimorphism
Cellular Molecular and Biomedical Reports,
Год журнала:
2023,
Номер
4(2), С. 88 - 99
Опубликована: Окт. 10, 2023
Abnormalities
of
several
oncogenes
and
tumor
suppressor
genes
have
been
identified
in
carcinomas
during
the
last
decade
pathological
warfare
physiological
traits,
multiple
genetic
changes
demonstrated
individual
carcinomas.
We
conducted
a
systematic
review
studies
enrolling
adolescents
adults
with
Carcinoma,
every
type
which
cancer
intervention
was
randomized,
or
all
study
designs
there
primary
secondary
outcome.
searched
Ovid
MEDLINE,
EMBASE,
Evidence-Based
Medicine
Reviews
from
1990
to
June
2015.
Two
reviewers
evaluated
eligibility
abstracted
data.
In
total,
67
were
included
consisted
62
randomized
trials,
reviews,
5
studies.
None
(0/81)
provided
definition.
Only
one
trial
unable
identify
any
definitions
used
Carcinoma.
Given
that
proportion
this
population
may
receive
intensive
treatment,
is
an
urgent
need
for
consensus-based
use
across
trials
&
meta-analysis.
