TY  - JOUR
AU  - Sakthivelu, Vignesh
AU  - Schmitt, Anna
AU  - Odenthal, Franka
AU  - Ndoci, Kristiano
AU  - Touet, Marian
AU  - Shaib, Ali H
AU  - Chihab, Abdulla
AU  - Wani, Gulzar A
AU  - Nieper, Pascal
AU  - Hartmann, Griffin G
AU  - Pintelon, Isabel
AU  - Kisis, Ilmars
AU  - Boecker, Maike
AU  - Eckert, Naja M
AU  - Ianicelli Caiaffa, Manoela
AU  - Ibruli, Olta
AU  - Weber, Julia
AU  - Maresch, Roman
AU  - Bebber, Christina M
AU  - Chitsaz, Ali
AU  - Lütz, Anna
AU  - Kim Alves Carpinteiro, Mira
AU  - Morris, Kaylee M
AU  - Franchino, Camilla A
AU  - Benz, Jonas
AU  - Pérez-Revuelta, Laura
AU  - Soriano-Campos, Jorge A
AU  - Huetzen, Maxim A
AU  - Goergens, Jonas
AU  - Jevtic, Milica
AU  - Jahn-Kelleter, Hannah M
AU  - Zempel, Hans
AU  - Placzek, Aleksandra
AU  - Hennrich, Alexandru A
AU  - Conzelmann, Karl-Klaus
AU  - Tumbrink, Hannah L
AU  - Hunold, Pascal
AU  - Isensee, Joerg
AU  - Werr, Lisa
AU  - Gaedke, Felix
AU  - Schauss, Astrid
AU  - Minère, Marielle
AU  - Müller, Marie
AU  - Fenselau, Henning
AU  - Liu, Yin
AU  - Heimsoeth, Alena
AU  - Gülcüler Balta, Gülce S
AU  - Walczak, Henning
AU  - Frezza, Christian
AU  - Jachimowicz, Ron D
AU  - George, Julie
AU  - Schmiel, Marcel
AU  - Brägelmann, Johannes
AU  - Hucho, Tim
AU  - von Karstedt, Silvia
AU  - Peifer, Martin
AU  - Annibaldi, Alessandro
AU  - Hänsel-Hertsch, Robert
AU  - Persigehl, Thorsten
AU  - Grüll, Holger
AU  - Sos, Martin
AU  - Reifenberger, Guido
AU  - Fischer, Matthias
AU  - Adriaensen, Dirk
AU  - Büttner, Reinhard
AU  - Sage, Julien
AU  - Brouns, Inge
AU  - Rad, Roland
AU  - Thomas, Roman K
AU  - Anstötz, Max
AU  - Rizzoli, Silvio O
AU  - Bergami, Matteo
AU  - Motori, Elisa
AU  - Reinhardt, Hans Christian
AU  - Beleggia, Filippo
TI  - Functional synapses between neurons and small cell lung cancer.
JO  - Nature
VL  - nn
SN  - 0028-0836
CY  - London [u.a.]
PB  - Nature Publ. Group
M1  - DKFZ-2025-01885
SP  - nn
PY  - 2025
N1  - epub
AB  - Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer, characterized by rapid proliferation, early metastatic spread, frequent early relapse and a high mortality rate1-3. Recent evidence has suggested that innervation has an important role in the development and progression of several types of cancer4,5. Cancer-to-neuron synapses have been reported in gliomas6,7, but whether peripheral tumours can form such structures is unknown. Here we show that SCLC cells can form functional synapses and receive synaptic transmission. Using in vivo insertional mutagenesis screening in conjunction with cross-species genomic and transcriptomic validation, we identified neuronal, synaptic and glutamatergic signalling gene sets in mouse and human SCLC. Further experiments revealed the ability of SCLC cells to form synaptic structures with neurons in vitro and in vivo. Electrophysiology and optogenetic experiments confirmed that cancer cells can receive NMDA receptor- and GABAA receptor-mediated synaptic inputs. Fitting with a potential oncogenic role of neuron-SCLC interactions, we showed that SCLC cells derive a proliferation advantage when co-cultured with vagal sensory or cortical neurons. Moreover, inhibition of glutamate signalling had therapeutic efficacy in an autochthonous mouse model of SCLC. Therefore, following malignant transformation, SCLC cells seem to hijack synaptic signalling to promote tumour growth, thereby exposing a new route for therapeutic intervention.
LB  - PUB:(DE-HGF)16
C6  - pmid:40931078
DO  - DOI:10.1038/s41586-025-09434-9
UR  - https://inrepo02.dkfz.de/record/304496
ER  -