Sensory neurons drive pancreatic cancer progression through glutamatergic neuron-cancer pseudo-synapses
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F25%3A00643828" target="_blank" >RIV/68378041:_____/25:00643828 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1016/j.ccell.2025.09.003" target="_blank" >https://doi.org/10.1016/j.ccell.2025.09.003</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ccell.2025.09.003" target="_blank" >10.1016/j.ccell.2025.09.003</a>
Alternative languages
Result language
angličtina
Original language name
Sensory neurons drive pancreatic cancer progression through glutamatergic neuron-cancer pseudo-synapses
Original language description
Cancers thrive on neuronal input. Here, we demonstrate the presence of pseudo-synaptic connections between sensory nerve endings and cancer cells in an extracerebral cancer, i.e., pancreatic ductal adenocarcinoma (PDAC). These synaptic sites exhibit a selective enrichment of the glutamatergic N-methyl-Daspartate receptor (NMDA) receptor subunit NMDAR2D (GRIN2D) on the cancer cells, which turns PDAC cells responsive to neuron-derived glutamate and promotes tumor growth and spread. Intriguingly, neurons transform a subset of co-cultured PDAC cells into calcium-responsive cells via GRIN2D-type glutamate receptors at the neuron-cancer pseudo-synapses. We found that the expression of this subunit is due to the increased glutamate availability provided by sensory innervation in a neurotrophic feedforward loop. Moreover, interference with the glutamate-GRIN2D signaling at these neuron-cancer pseudo-synapses markedly improved survival in vivo. This discovery of peripheral cancer-neuron pseudo-synapses may provide an opportunity for cancer-neuroscience-instructed oncological therapies.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cancer Cell
ISSN
1535-6108
e-ISSN
1878-3686
Volume of the periodical
43
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
27
Pages from-to
2241-2258
UT code for WoS article
001641117900004
EID of the result in the Scopus database
2-s2.0-105020812364