Cancers,
Год журнала:
2018,
Номер
10(1), С. 23 - 23
Опубликована: Янв. 19, 2018
The
mammalian
Target
of
Rapamycin
(mTOR)
pathway
plays
an
essential
role
in
sensing
and
integrating
a
variety
exogenous
cues
to
regulate
cellular
growth
metabolism,
both
physiological
pathological
conditions.
mTOR
functions
through
two
functionally
structurally
distinct
multi-component
complexes,
mTORC1
mTORC2,
which
interact
with
each
other
several
elements
signaling
pathways.
In
the
past
few
years,
many
new
insights
into
function
regulation
have
been
gained
extensive
genetic
pharmacological
studies
mice
enhanced
our
understanding
how
dysfunction
contributes
diseases,
including
cancer.
Single-agent
targeting,
mostly
using
rapalogs,
has
so
far
met
limited
clinical
success;
however,
due
cross-talk
between
pathways,
combined
approaches
are
most
promising
avenues
improve
efficacy
available
therapeutics
overcome
drug
resistance.
This
review
provides
brief
up-to-date
narrative
on
function,
relative
contributions
mTORC2
complexes
cancer
development
progression,
prospects
for
inhibition
as
therapeutic
strategy.
Frontiers in Cell and Developmental Biology,
Год журнала:
2018,
Номер
6
Опубликована: Сен. 10, 2018
Low
oxygen
availability,
a
condition
known
as
hypoxia,
is
common
feature
of
various
pathologies
including
stroke,
ischemic
heart
disease,
and
cancer.
Hypoxia
adaptation
requires
coordination
intricate
pathways
mechanisms
such
hypoxia-inducible
factors
(HIFs),
the
unfolded
protein
response
(UPR),
mTOR,
autophagy.
Recently,
great
effort
has
been
invested
toward
elucidating
interplay
between
hypoxia-induced
autophagy
cancer
cell
metabolism.
Although
novel
types
selective
have
identified,
mitophagy,
pexophagy,
lipophagy,
ERphagy
nucleophagy
among
others,
their
potential
interface
with
hypoxia
remains
poorly
understood.
Autophagy
activation
facilitates
removal
damaged
cellular
compartments
recycles
components,
thus
promoting
survival.
Importantly,
tumor
cells
rely
on
to
support
self-proliferation
metastasis;
characteristics
related
poor
disease
prognosis.
Therefore,
deeper
understanding
molecular
crosstalk
could
provide
important
insights
relevance
hypoxia-related
pathologies.
Here,
we
survey
recent
findings
implicating
in
hypoxic
responses,
discuss
emerging
links
these
pathophysiology.
Cancers,
Год журнала:
2018,
Номер
10(1), С. 23 - 23
Опубликована: Янв. 19, 2018
The
mammalian
Target
of
Rapamycin
(mTOR)
pathway
plays
an
essential
role
in
sensing
and
integrating
a
variety
exogenous
cues
to
regulate
cellular
growth
metabolism,
both
physiological
pathological
conditions.
mTOR
functions
through
two
functionally
structurally
distinct
multi-component
complexes,
mTORC1
mTORC2,
which
interact
with
each
other
several
elements
signaling
pathways.
In
the
past
few
years,
many
new
insights
into
function
regulation
have
been
gained
extensive
genetic
pharmacological
studies
mice
enhanced
our
understanding
how
dysfunction
contributes
diseases,
including
cancer.
Single-agent
targeting,
mostly
using
rapalogs,
has
so
far
met
limited
clinical
success;
however,
due
cross-talk
between
pathways,
combined
approaches
are
most
promising
avenues
improve
efficacy
available
therapeutics
overcome
drug
resistance.
This
review
provides
brief
up-to-date
narrative
on
function,
relative
contributions
mTORC2
complexes
cancer
development
progression,
prospects
for
inhibition
as
therapeutic
strategy.
