Frontiers in Endocrinology,
Journal Year:
2016,
Volume and Issue:
6
Published: Jan. 11, 2016
The
phosphatidylinositol
3-kinase
(PI3K)/Akt
pathway
is
a
key
driver
in
carcinogenesis.
Defects
this
human
cancer
syndromes
such
as
Cowden's
disease
and
Multiple
Endocrine
Neoplasia
result
tumors
of
endocrine
tissues,
highlighting
its
importance
these
types.
This
review
explores
the
growing
evidence
from
multiple
animal
vitro
models
analysis
for
involvement
following:
thyroid
carcinoma
subtypes,
parathyroid
carcinoma,
pituitary
tumors,
adrenocortical
phaeochromocytoma,
neuroblastoma,
gastroenteropancreatic
neuroendocrine
tumors.
Whilst
data
are
not
always
consistent,
immunohistochemistry
performed
on
tumor
tissue
has
been
used
alongside
other
techniques
to
demonstrate
Akt
overactivation.
We
active
potential
prognostic
marker
PI3K
therapeutic
target
neoplasia.
International Journal of Molecular Sciences,
Journal Year:
2020,
Volume and Issue:
21(11), P. 3904 - 3904
Published: May 30, 2020
The
Wnt
signaling
pathway
plays
important
roles
in
embryonic
development,
homeostatic
processes,
cell
differentiation,
polarity,
proliferation,
and
migration
via
the
β-catenin
binding
of
target
genes.
Dysregulation
is
associated
with
various
diseases
such
as
cancer,
aging,
Alzheimer's
disease,
metabolic
pigmentation
disorders.
Numerous
studies
entailing
have
been
conducted
for
cancers.
Diverse
factors
mediate
up-
or
down-regulation
through
post-translational
modifications
(PTMs),
aberrant
regulation
several
different
malignancies
humans.
Of
numerous
PTMs
involved,
most
are
regulated
by
ubiquitination
deubiquitination.
Ubiquitination
E3
ligase
attaches
ubiquitins
to
proteins
usually
induces
proteasomal
degradation
β-catenin,
Axin,
GSK3,
Dvl.
Conversely,
deubiquitination
induced
deubiquitinating
enzymes
(DUBs)
detaches
modulates
stability
factors.
In
this
review,
we
discuss
effects
on
pathway,
inhibitors
DUBs
that
can
be
applied
cancer
therapeutic
strategies.
British Journal of Clinical Pharmacology,
Journal Year:
2016,
Volume and Issue:
82(5), P. 1189 - 1212
Published: April 10, 2016
Rapamycin
and
modified
rapamycins
(rapalogs)
have
been
used
to
prevent
allograft
rejection
after
organ
transplant
for
over
15
years.
The
mechanistic
target
of
rapamycin
(mTOR)
has
determined
be
a
key
component
the
mTORC1
complex
which
consists
serine/threonine
kinase
TOR
at
least
five
other
proteins
are
involved
in
regulating
its
activity.
Some
best
characterized
substrates
kinases
regulation
cell
growth
(e.g.,
p70S6K)
protein
translation
4E‐BP1).
These
may
some
cases
serve
as
indicators
sensitivity
rapamycin‐related
therapies.
Dysregulation
activity
frequently
occurs
due
mutations
at,
or
amplifications
of,
upstream
factor
receptors
human
epidermal
receptor‐2,
HER2)
well
PI3K)
phosphatases
PTEN)
critical
growth.
More
recently,
it
shown
that
certain
rapalogs
enhance
effectiveness
hormonal‐based
therapies
breast
cancer
patients
who
become
resistant
endocrine
therapy.
combined
treatment
everolimus)
aromatase
inhibitors
exemestane)
approved
by
United
States
Food
Drug
Administration
(US
FDA)
drug
regulatory
agencies
treat
estrogen
receptor
positive
(ER+)
progressed.
This
review
will
summarize
recent
basic
clinical
research
area
evaluate
potential
novel
therapeutic
approaches.
Aberrant
activation
of
Wnt/β-catenin
signaling
plays
an
unequivocal
role
in
colorectal
cancer,
but
identification
effective
Wnt
inhibitors
for
use
cancer
remains
a
tremendous
challenge.
New
insights
into
the
regulation
this
pathway
could
reveal
new
therapeutic
point
intervention,
therefore
are
greatly
needed.
Here
we
report
novel
FAK/PYK2/GSK3βY216/β-catenin
axis:
FAK
and
PYK2,
elevated
adenomas
APCmin/+
mice
human
tissues,
functioned
redundantly
to
promote
by
phosphorylating
GSK3βY216
reinforce
output—β-catenin
accumulation
intestinal
tumorigenesis.
We
previously
showed
that
Wnt-induced
β-catenin
requires
GSK3β/β-TrCP
interaction;
current
study
revealed
phosphorylation
was
molecular
determinant
GSK3β
recruitment
β-TrCP.
Pharmacological
inhibition
FAK/PYK2
suppressed
adenoma
formation
accompanied
with
reduced
levels
phospho-GSK3βY216
β-catenin,
indicating
FAK/PYK2/GSK3βY216
axis
is
critical
APC
driven
Frontiers in Endocrinology,
Journal Year:
2016,
Volume and Issue:
6
Published: Jan. 11, 2016
The
phosphatidylinositol
3-kinase
(PI3K)/Akt
pathway
is
a
key
driver
in
carcinogenesis.
Defects
this
human
cancer
syndromes
such
as
Cowden's
disease
and
Multiple
Endocrine
Neoplasia
result
tumors
of
endocrine
tissues,
highlighting
its
importance
these
types.
This
review
explores
the
growing
evidence
from
multiple
animal
vitro
models
analysis
for
involvement
following:
thyroid
carcinoma
subtypes,
parathyroid
carcinoma,
pituitary
tumors,
adrenocortical
phaeochromocytoma,
neuroblastoma,
gastroenteropancreatic
neuroendocrine
tumors.
Whilst
data
are
not
always
consistent,
immunohistochemistry
performed
on
tumor
tissue
has
been
used
alongside
other
techniques
to
demonstrate
Akt
overactivation.
We
active
potential
prognostic
marker
PI3K
therapeutic
target
neoplasia.
