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@ARTICLE{Sakthivelu:304496,
author = {V. Sakthivelu and A. Schmitt and F. Odenthal and K. Ndoci
and M. Touet and A. H. Shaib and A. Chihab and G. A. Wani
and P. Nieper and G. G. Hartmann and I. Pintelon and I.
Kisis and M. Boecker and N. M. Eckert and M. Ianicelli
Caiaffa and O. Ibruli and J. Weber and R. Maresch and C. M.
Bebber and A. Chitsaz and A. Lütz and M. Kim Alves
Carpinteiro and K. M. Morris and C. A. Franchino and J. Benz
and L. Pérez-Revuelta and J. A. Soriano-Campos and M. A.
Huetzen and J. Goergens and M. Jevtic and H. M.
Jahn-Kelleter and H. Zempel and A. Placzek and A. A.
Hennrich and K.-K. Conzelmann and H. L. Tumbrink and P.
Hunold and J. Isensee and L. Werr and F. Gaedke and A.
Schauss and M. Minère and M. Müller and H. Fenselau and Y.
Liu and A. Heimsoeth and G. S. Gülcüler Balta and H.
Walczak and C. Frezza and R. D. Jachimowicz and J. George
and M. Schmiel and J. Brägelmann and T. Hucho and S. von
Karstedt and M. Peifer and A. Annibaldi and R.
Hänsel-Hertsch and T. Persigehl and H. Grüll and M.
Sos$^*$ and G. Reifenberger and M. Fischer and D. Adriaensen
and R. Büttner and J. Sage and I. Brouns and R. Rad and R.
K. Thomas and M. Anstötz and S. O. Rizzoli and M. Bergami
and E. Motori and H. C. Reinhardt$^*$ and F. Beleggia},
title = {{F}unctional synapses between neurons and small cell lung
cancer.},
journal = {Nature},
volume = {nn},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2025-01885},
pages = {nn},
year = {2025},
note = {epub},
abstract = {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.},
cin = {MU01 / ED01},
ddc = {500},
cid = {I:(DE-He78)MU01-20160331 / I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40931078},
doi = {10.1038/s41586-025-09434-9},
url = {https://inrepo02.dkfz.de/record/304496},
}