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000304496 1001_ $$00009-0000-1652-0850$$aSakthivelu, Vignesh$$b0
000304496 245__ $$aFunctional synapses between neurons and small cell lung cancer.
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000304496 520__ $$aSmall cell lung cancer (SCLC) is a highly aggressive type of lung cancer, characterized by rapid proliferation, early metastatic spread, frequent early relapse and a high mortality rate1-3. Recent evidence has suggested that innervation has an important role in the development and progression of several types of cancer4,5. Cancer-to-neuron synapses have been reported in gliomas6,7, but whether peripheral tumours can form such structures is unknown. Here we show that SCLC cells can form functional synapses and receive synaptic transmission. Using in vivo insertional mutagenesis screening in conjunction with cross-species genomic and transcriptomic validation, we identified neuronal, synaptic and glutamatergic signalling gene sets in mouse and human SCLC. Further experiments revealed the ability of SCLC cells to form synaptic structures with neurons in vitro and in vivo. Electrophysiology and optogenetic experiments confirmed that cancer cells can receive NMDA receptor- and GABAA receptor-mediated synaptic inputs. Fitting with a potential oncogenic role of neuron-SCLC interactions, we showed that SCLC cells derive a proliferation advantage when co-cultured with vagal sensory or cortical neurons. Moreover, inhibition of glutamate signalling had therapeutic efficacy in an autochthonous mouse model of SCLC. Therefore, following malignant transformation, SCLC cells seem to hijack synaptic signalling to promote tumour growth, thereby exposing a new route for therapeutic intervention.
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000304496 7001_ $$aSchmitt, Anna$$b1
000304496 7001_ $$00000-0003-4138-121X$$aOdenthal, Franka$$b2
000304496 7001_ $$00000-0002-9896-8196$$aNdoci, Kristiano$$b3
000304496 7001_ $$00009-0004-7875-1880$$aTouet, Marian$$b4
000304496 7001_ $$aShaib, Ali H$$b5
000304496 7001_ $$00009-0002-1237-0087$$aChihab, Abdulla$$b6
000304496 7001_ $$00000-0003-2380-5816$$aWani, Gulzar A$$b7
000304496 7001_ $$aNieper, Pascal$$b8
000304496 7001_ $$00000-0001-9213-8995$$aHartmann, Griffin G$$b9
000304496 7001_ $$aPintelon, Isabel$$b10
000304496 7001_ $$00000-0001-6207-3991$$aKisis, Ilmars$$b11
000304496 7001_ $$00009-0008-0595-8599$$aBoecker, Maike$$b12
000304496 7001_ $$00009-0007-2888-0280$$aEckert, Naja M$$b13
000304496 7001_ $$00009-0007-0704-0397$$aIanicelli Caiaffa, Manoela$$b14
000304496 7001_ $$aIbruli, Olta$$b15
000304496 7001_ $$aWeber, Julia$$b16
000304496 7001_ $$aMaresch, Roman$$b17
000304496 7001_ $$00000-0002-7841-7493$$aBebber, Christina M$$b18
000304496 7001_ $$aChitsaz, Ali$$b19
000304496 7001_ $$00009-0000-2891-7038$$aLütz, Anna$$b20
000304496 7001_ $$aKim Alves Carpinteiro, Mira$$b21
000304496 7001_ $$aMorris, Kaylee M$$b22
000304496 7001_ $$aFranchino, Camilla A$$b23
000304496 7001_ $$aBenz, Jonas$$b24
000304496 7001_ $$aPérez-Revuelta, Laura$$b25
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000304496 7001_ $$00000-0002-7510-3077$$aZempel, Hans$$b31
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