MCT1 lactate transporter blockade re-invigorates anti-tumor immunity through metabolic rewiring of dendritic cells in melanoma
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Янв. 27, 2025
Язык: Английский
Crystallographic Structure and Antiglioma Potential of Centrolobium microchaete Seed Lectin
ACS Omega,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 27, 2025
The
genus
Centrolobium
comprises
species
of
Neotropical
trees
with
seeds
that
possess
medicinal
and
bioactive
applications.
Lectins
from
this
exhibit
anti-inflammatory
immunomodulatory
effects,
influencing
the
activation
immune
system.
This
study
focuses
on
characterizing
structure
carbohydrate-binding
properties
lectin
microchaete
(CML)
evaluating
its
potential
against
gliomas.
in
complex
methyl-mannose-α1,3-mannose
(MDM)
was
resolved
using
X-ray
crystallography
at
1.3
Å
resolution,
interactions
further
analyzed
through
molecular
dynamics
simulations.
Structurally,
CML
adopts
a
β-sandwich
motif
assembles
into
canonical
dimers.
In
vitro
assays
revealed
reduced
viability
C6
glioma
cells,
although
only
high
concentrations,
without
impacting
cell
migration
or
morphology.
activated
autophagic
processes,
albeit
lower
efficacy
compared
other
mannose-specific
lectins.
limited
antiglioma
activity
may
be
linked
to
inability
form
tetramers
unusual
specificity
toward
asymmetric
glycans,
both
crucial
features
for
cellular
glycans
signaling
pathways.
represents
first
investigation
Dalbergieae
tribe,
highlighting
structural
characteristics
functional
limitations.
Язык: Английский
Melanoma Glycome Regulates the Pro-Oncogenic Properties of Extracellular Galectin-3
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(10), С. 4882 - 4882
Опубликована: Май 19, 2025
Metastatic
melanoma
is
an
aggressive
skin
cancer
with
a
five-year
survival
rate
of
only
35%.
Despite
recent
advances
in
immunotherapy,
there
still
urgent
need
for
the
development
innovative
therapeutic
approaches
to
improve
clinical
outcomes
patients
metastatic
melanoma.
Prior
research
from
our
laboratory
revealed
that
loss
I-branching
enzyme
β1,6
N-acetylglucosaminyltransferase
2
(GCNT2),
consequent
substitution
surface
I-branched
poly-N-acetyllactosamines
(poly-LacNAcs)
i-linear
poly-LacNAcs,
implicated
driving
metastasis.
In
current
study,
we
explored
role
galectin-3
(Gal-3),
lectin
avidly
binds
dictating
behavior.
Our
results
show
Gal-3
favors
binding
while
enforced
GCNT2/I-branching
disrupts
this
interaction,
thereby
suppressing
Gal-3-dependent
malignant
characteristics,
including
extracellular
signal-regulated
kinase/mitogen-activated
protein
kinase
(ERK/MAPK)
pathway
activation,
BCL2
expression,
cell
proliferation,
and
migration.
This
report
establishes
crucial
interactions
glycans
promoting
aggressiveness,
placing
GCNT2
as
tumor
suppressor
suggesting
both
potential
targets
Язык: Английский