Institute for Translational Medicine, the Affiliated Hospital of Qingdao University, Medical College, Qingdao University, 266021, Qingdao, China.
Department of Urology, Qingdao Municipal Hospital Affiliated to Qingdao University, 266011, Qingdao, China.
Br J Cancer. 2022 Oct;127(7):1184-1192. doi: 10.1038/s41416-022-01863-x. Epub 2022 May 27.
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.
过去十年的研究揭示了神经系统在肿瘤微环境中的重要作用。癌症神经科学的最新进展，特别是神经元-肿瘤突触/突触周结构的发现，揭示了突触蛋白在脑肿瘤进展中的黑暗面。在这里，我们提供了肿瘤细胞表达的突触蛋白概述，并通过将其与神经元突触蛋白进行比较，分析了它们的分子功能和组织。我们重点研究了 neuroligin-3、谷氨酸受体 AMPAR 和 NMDAR 以及突触支架蛋白 DLGAP1，因为它们在肿瘤增殖和进展中的新发现的调节作用。癌症神经科学的进展为癌症治疗带来了新的见解。在这篇综述的最后一部分，我们讨论了针对突触蛋白的治疗策略，以及针对其在癌症治疗中的临床应用的当前挑战和可能的工具包。我们对癌症神经科学的理解还处于初级阶段；更深入地研究肿瘤细胞如何利用突触信号将有助于发挥突触蛋白作为有前途的抗肿瘤靶点的治疗潜力。
