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Cellular and Molecular Biology

The dark side of synaptic proteins in tumours

British Journal of Cancer volume 127, pages 1184–1192 (2022)Cite this article

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Abstract

Research in the past decade has uncovered the essential role of the nervous system in the tumour microenvironment. The recent advances in cancer neuroscience, especially the discovery of neuron–tumour synaptic/perisynaptic structures, have revealed the dark side of synaptic proteins in the progression of brain tumours. Here, we provide an overview of the synaptic proteins expressed by tumour cells and analyse their molecular functions and organisation by comparing them with neuronal synaptic proteins. We focus on the studies of neuroligin-3, the glutamate receptors AMPAR and NMDAR and the synaptic scaffold protein DLGAP1, for their newly discovered regulatory role in the proliferation and progression of tumours. Progress in cancer neuroscience has brought novel insights into the treatment of cancers. In the last part of this review, we discuss the therapeutical strategies targeting synaptic proteins and the current challenges and possible toolkits regarding their clinical application in cancer treatment. Our understanding of cancer neuroscience is still in its infancy; deeper investigation of how tumour cells co-opt synaptic signaling will help fulfil the therapeutical potential of the synaptic proteins as promising anti-tumour targets.

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Fig. 1: Interactions between the nervous system and tumours.
Fig. 2: An overview of synaptic proteins expressed in glioma cells.
Fig. 3: Extracellular soluble neuroligin-3 acts as a mitogen to promote glioma cell proliferation.

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Data availability

The statistical data for Fig. 2a are available upon request.

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Acknowledgements

We thank the support from the International Research Centre for Non-coding RNAs and Translational Medicine, Qingdao.

Funding

This work was supported by the National Natural Science Foundation of China (No. 32101020 and 91849209), Natural Science Foundation of Shandong Province (CN) (No. ZR2020MC071 and ZR2019LZL001) and the People's Livelihood Science and Technology Project of Qingdao (CN) (No. 20-3-4-41-nsh).

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  1. Institute for Translational Medicine, the Affiliated Hospital of Qingdao University, Medical College, Qingdao University, 266021, Qingdao, China

    Jing Li, Yalan Xu, Yin Wang, Peifeng Li & Dong Wang

  2. Department of Urology, Qingdao Municipal Hospital Affiliated to Qingdao University, 266011, Qingdao, China

    Hai Zhu

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  1. Jing Li
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JL conceived the manuscript, JL, YX and HZ wrote the manuscript, YX and DW drew the figures, DW, YW and PL revised the manuscript.

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Correspondence to Jing Li.

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Li, J., Xu, Y., Zhu, H. et al. The dark side of synaptic proteins in tumours. Br J Cancer 127, 1184–1192 (2022). https://doi.org/10.1038/s41416-022-01863-x

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