Frontiers in Oncology,
Год журнала:
2024,
Номер
14
Опубликована: Март 25, 2024
Altered
lipid
metabolism
is
a
well-recognized
feature
of
solid
cancers,
including
colorectal
cancer.
In
cancer,
upregulation
contributes
to
initiation,
progression,
and
metastasis;
thus,
aberrant
poor
patient
outcome.
The
inactivating
mutation
APC
,
vital
tumor
suppressor
in
the
Wnt
signaling
pathway,
key
event
that
occurs
early
majority
cancer
cases.
potential
crosstalk
between
APC-driven
poorly
understood.
This
review
collectively
highlights
summarizes
limited
understanding
mutations
Wnt/beta-catenin
metabolism.
interconnection
inactivation
activates
which
causes
transcriptome,
epigenetic,
microbiome
changes
promote
initiation
progression.
Furthermore,
downstream
effects
this
collaborative
effort
are
enhanced
stemness,
cellular
proliferation,
prooncogenic
signaling,
survival.
Understanding
mechanistic
link
alterations
may
foster
identification
new
therapeutic
targets
enable
development
more
efficacious
strategies
for
prevention
and/or
treatment
Nature,
Год журнала:
2022,
Номер
611(7937), С. 744 - 753
Опубликована: Окт. 26, 2022
Abstract
Genetic
and
epigenetic
variation,
together
with
transcriptional
plasticity,
contribute
to
intratumour
heterogeneity
1
.
The
interplay
of
these
biological
processes
their
respective
contributions
tumour
evolution
remain
unknown.
Here
we
show
that
genetic
ancestry
only
infrequently
affects
gene
expression
traits
subclonal
in
colorectal
cancer
(CRC).
Using
spatially
resolved
paired
whole-genome
transcriptome
sequencing,
find
the
majority
variation
is
not
strongly
heritable
but
rather
‘plastic’.
Somatic
quantitative
trait
loci
analysis
identified
a
number
putative
controls
by
cis
-acting
coding
non-coding
mutations,
which
were
clonal
within
tumour,
alongside
frequent
structural
alterations.
Consistently,
computational
inference
on
spatial
patterning
phylogenies
finds
considerable
proportion
CRCs
did
evidence
selection,
subset
drivers
associated
subclone
expansions.
Spatial
intermixing
clones
common,
some
tumours
growing
exponentially
others
at
periphery.
Together,
our
data
suggest
most
CRC
has
no
major
phenotypic
consequence
plasticity
is,
instead,
widespread
tumour.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Июнь 18, 2024
Abstract
Tumorigenesis
is
a
multistep
process,
with
oncogenic
mutations
in
normal
cell
conferring
clonal
advantage
as
the
initial
event.
However,
despite
pervasive
somatic
and
expansion
tissues,
their
transformation
into
cancer
remains
rare
event,
indicating
presence
of
additional
driver
events
for
progression
to
an
irreversible,
highly
heterogeneous,
invasive
lesion.
Recently,
researchers
are
emphasizing
mechanisms
environmental
tumor
risk
factors
epigenetic
alterations
that
profoundly
influencing
early
malignant
evolution,
independently
inducing
mutations.
Additionally,
evolution
tumorigenesis
reflects
multifaceted
interplay
between
cell-intrinsic
identities
various
cell-extrinsic
exert
selective
pressures
either
restrain
uncontrolled
proliferation
or
allow
specific
clones
progress
tumors.
by
which
induce
both
intrinsic
cellular
competency
remodel
stress
facilitate
not
fully
understood.
In
this
review,
we
summarize
genetic,
epigenetic,
external
events,
effects
on
co-evolution
transformed
cells
ecosystem
during
initiation
evolution.
A
deeper
understanding
earliest
molecular
holds
promise
translational
applications,
predicting
individuals
at
high-risk
developing
strategies
intercept
transformation.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Ноя. 29, 2023
Abstract
The
dominant
mutational
signature
in
colorectal
cancer
genomes
is
C
>
T
deamination
(COSMIC
Signature
1)
and,
a
small
subgroup,
mismatch
repair
signatures
6
and
44).
Mutations
common
driver
genes
are
often
not
consistent
with
those
signatures.
Here
we
perform
whole-genome
sequencing
of
normal
colon
crypts
from
patients,
matched
to
previous
multi-omic
tumour
dataset.
We
analyse
that
were
distant
vs
adjacent
the
cancer.
In
contrast
healthy
individuals,
patients
have
high
incidence
pks
+
(polyketide
synthases)
E.coli
(
Escherichia
coli
)
indel
signatures,
this
confirmed
by
metagenomics.
These
compatible
many
clonal
mutations
detected
corresponding
samples,
including
chromatin
modifier
genes,
supporting
their
role
early
tumourigenesis.
results
provide
evidence
potential
carcinogenesis
human
gut.
Cancer Discovery,
Год журнала:
2024,
Номер
14(5), С. 866 - 889
Опубликована: Март 26, 2024
Abstract
Patients
with
estrogen
receptor–positive
breast
cancer
receive
adjuvant
endocrine
therapies
(ET)
that
delay
relapse
by
targeting
clinically
undetectable
micrometastatic
deposits.
Yet,
up
to
50%
of
patients
even
decades
after
surgery
through
unknown
mechanisms
likely
involving
dormancy.
To
investigate
genetic
and
transcriptional
changes
underlying
tumor
awakening,
we
analyzed
late
longitudinally
profiled
a
rare
cohort
treated
long-term
neoadjuvant
ETs
until
progression.
Next,
developed
an
in
vitro
evolutionary
study
record
the
adaptive
strategies
individual
lineages
unperturbed
parallel
experiments.
Our
data
demonstrate
induce
nongenetic
cell
state
transitions
into
dormancy
stochastic
subset
cells
via
epigenetic
reprogramming.
Single
divergent
phenotypes
awaken
unpredictably
absence
recurrent
alterations.
Targeting
dormant
epigenome
shows
promising
activity
against
adapting
cells.
Overall,
this
uncovers
contribution
adaptation
evolution
resistance
ETs.
Significance:
This
advances
understanding
therapy-induced
potential
clinical
implications
for
cancer.
Estrogen
receptor-positive
adapt
treatment
entering
characterized
strong
heterochromatinization
no
changes.
rewiring
impairs
See
related
commentary
Llinas-Bertran
et
al.,
p.
704.
article
is
featured
Selected
Articles
from
Issue,
695
Cell Reports,
Год журнала:
2024,
Номер
43(3), С. 113912 - 113912
Опубликована: Март 1, 2024
In
this
study,
we
explore
the
dynamic
process
of
colorectal
cancer
progression,
emphasizing
evolution
toward
a
more
metastatic
phenotype.
The
term
"evolution"
as
used
in
study
specifically
denotes
phenotypic
transition
higher
potency
from
well-formed
glandular
structures
to
collective
invasion,
ultimately
resulting
development
cell
buddings
at
invasive
front.
Our
findings
highlight
spatial
correlation
with
tumor
senescence,
revealing
distinct
types
senescent
cells
(types
I
and
II)
that
play
different
roles
overall
progression.
Type
(p16INK4A+/CXCL12+/LAMC2−/MMP7−)
are
identified
invasion
region,
whereas
type
II
(p16INK4A+/CXCL12+/LAMC2+/MMP7+),
representing
final
evolved
form,
prominently
located
partial-EMT
region.
Importantly,
associate
local
lymph
node
metastasis
cancer,
potentially
affecting
patient
prognosis.
