P-cadherin overexpression is associated with early transformation of the Fallopian tube epithelium and aggressiveness of tubo-ovarian high-grade serous carcinoma
Virchows Archiv,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 5, 2025
Abstract
Tubo-ovarian
high-grade
serous
carcinoma
(HGSC)
with
proficient
homologous
recombination
(HR)
DNA
repair
(HRP)
accounts
for
approximately
50%
of
cases
and
is
associated
platinum-resistance
poor
prognosis.
We
hypothesize
that
the
acquisition
hybrid
phenotypes
displaying
both
epithelial
mesenchymal
(E/M)
features
may
be
involved
in
malignant
transformation
tumour
dissemination
this
subgroup.
Therefore,
we
analysed,
by
digital
pathology,
expression
prognostic
significance
3
classic
cadherins
(E-cadherin,
marker;
N-cadherin,
P-cadherin,
candidate
marker
E/M)
577
formalin-fixed
paraffin-embedded
human
samples
representing
putative
stepwise
carcinogenesis
Fallopian
tube
epithelium
(FTE).
observed
a
non-canonical
N-to-P-cadherin
switch
along
carcinogenic
progression,
statistically
significant
overexpression
P-cadherin
pre-malignant
samples,
compared
to
control
FTE.
Interestingly,
was
most
pronounced
precursor
lesions
HGSC
cells
from
ascites.
Tumours
high
were
significantly
worse
overall
survival,
especially
subgroup
without
BRCA1/2
mutations.
Transient
knock-down
resulted
vitro
reduction
functional
E/M
hallmarks,
namely
decreased
anoikis
resistance,
reduced
collective
migration
invasion
representative
platinum-resistant
HRP
cell
line.
Taken
together,
our
results
suggest
an
early
event
activation
HRP-HGSC,
further
supporting
adhesion
molecule
as
promising
biomarker
Language: Английский
Metformin Impairs Linsitinib Anti-Tumor Effect on Ovarian Cancer Cell Lines
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(22), P. 11935 - 11935
Published: Nov. 6, 2024
Ovarian
cancer
(OC)
remains
one
of
the
leading
causes
cancer-related
mortality
among
women.
Targeting
insulin-like
growth
factor
1
(IGF-1)
signaling
pathway
has
emerged
as
a
promising
therapeutic
strategy.
Linsitinib,
an
IGF-1
receptor
(IGF-1R)
inhibitor,
shown
potential
in
disrupting
this
pathway.
Additionally,
metformin,
commonly
used
treatment
type
2
diabetes,
been
studied
for
its
anti-cancer
properties
due
to
ability
inhibit
metabolic
pathways
that
intersect
with
signaling,
making
it
candidate
combination
therapy
treatments.
This
study
explores
effects
linsitinib
and
metformin
on
OVCAR3
cells
by
suppression
siRNA-mediated
Language: Английский