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A malignant symbiosis: The neuro-metabolic symphony rewires the tumor microenvironment
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DOI：10.1016/j.neo.2026.101322.png)
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Abstract
En 中文
• Neural signals actively orchestrate tumor metabolic reprogramming in the TME. • Tumor metabolites act as signaling mediators to alter neuronal plasticity. • A bidirectional neuro-metabolic loop drives cancer progression and resistance. • Co-targeting the neuro-metabolic axis offers a precision oncology paradigm.
Keywords:
Cancer neuroscience
Neuro-metabolism
Tumor microenvironment
Metabolic reprogramming
Neurotransmitters
TME
tumor microenvironment
FAO
fatty acid oxidation
GABA
gamma-aminobutyric acid
5-HT
serotonin
DA
dopamine
IDH
isocitrate dehydrogenase
NE
norepinephrine
EPI
epinephrine
CREB
cAMP Response Element-Binding Protein
ADRB2
β2-adrenergic receptor
CRC
colorectal cancer
MAOA
monoamine oxidase A
MAOB
monoamine oxidase B
TCA
tricarboxylic acid
ATGL
adipose triglyceride lipase
CPT1A
carnitine palmitoyltransferase 1A
MDSCs
myelooid-derived suppressor cells
HCC
hepatocellular carcinoma
USP2
ubiquitin-specific protease 2
ADRA2A
α2A-adrenergic receptor
cAMP
cyclic AMP
JNK
c-Jun N-terminal kinase
nAChRs
nicotinic acetylcholine receptors
mAChRs
muscarinic acetylcholine receptors
ACh
acetylcholine
HIF-1α
hypoxia-inducible factor 1α
ATP
adenosine triphosphate
Ca2+
calcium
NNK
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone
HNSCC
head and neck squamous cell carcinoma
CES1
carboxylesterase 1
GSH
glutathione
ROS
reactive oxygen species
AMPK
AMP-activated protein kinase
PET
positron emission tomography
GPCRs
G protein-coupled receptors
NK3R
neurokinin-3 receptor
MC1R
melanocortin 1 receptor
Tregs
regulatory T cells
NTSR1
neurotensin receptor 1
GLS1
Glutaminase 1
GPX4
glutathione peroxidase 4
SLC1A1
solute carrier family 1 member 1
GLUD1
glutamate dehydrogenase 1
SLC1A5
solute carrier family 1 member 5
NMDAR2B
N-methyl-D-aspartate receptor subunit 2B
EZH2
enhancer of zeste homolog 2
CCL2
CC motif chemokine ligand 2
BBB
blood-brain barrier
SIRT4
sirtuin 4
GLT-1
glial high affinity glutamate transporter 1
NF-κB
nuclear factor kappa-light-chain-enhancer of activated B cells
IL-8
interleukin 8
MAPK
mitogen-activated protein kinase
SLC7A11
solute carrier family 7 member 11
GAD1
glutamate decarboxylase 1
c-Myc
MYC proto-oncogene, cellular
EMT
epithelial-mesenchymal transition
FOXA2
factor forkhead box A2
GAT3
GABA transporter 3
PMCA4
plasma membrane Ca2+-ATPase 4
HTR2B
5-Hydroxytryptamine receptor 2B
HTR7
5-Hydroxytryptamine receptor 7
DRD2
D2 receptor
DRD1
D1 receptor
TAMs
tumor-associated macrophages
GCs
Glucocorticoids
TSCC
tongue squamous cell carcinoma
MET
mesenchymal-epithelial transition factor
T3
Triiodothyronine
ERAD
endoplasmic reticulum-associated degradation
ER
endoplasmic reticulum
CNS
central nervous systems
PNS
peripheral nervous systems
PNI
perineural invasion
SLC16A7
solute carrier family 16 member 7
MCT1
monocarboxylate transporter 1
NDRG3
N-Myc downstream regulated gene 3
MRI
magnetic resonance imaging
GBM
glioblastoma
IL-1β
interleukin-1β
PGE2
prostaglandin E2
AML
acute myeloid leukemia
D-2-HG
D-2-hydroxyglutarate
A2AR
A2A receptor
BTB
blood-tumor barrier
SAM
S-adenosylmethionine
METTL14
methyltransferase like 14
KP
kynurenine pathway
KMO
kynurenine 3-monooxygenase
ICC
intrahepatic cholangiocarcinoma
CCA
cholangiocarcinoma
USP1
ubiquitin-specific peptidase 1
B-ALL
B-cell acute lymphoblastic leukemia
SUMO
small ubiquitin-like modifier
ENO1
α-enolase
NKA
Na+/K+-ATPase
EAATs
excitatory amino acid transporters
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