Fig. 1

Synaptic communication and neuronal activity promotes glioma and brain metastasis. (1) Direct synaptic communication between neurons and cancer cells dictates glioma proliferation. Glutamate released by the neurons are taken up by glioma cells with upregulated AMPAR expression. (2) Tripartite-like synapses between neurons and breast cancer brain metastatic cells have also been reported as an indirect method of neuronal-cancer cell communication. Glutamate released by the neurons is taken up the proximal breast cancer brain metastatic cells through an NMDAR mediated pathway, promoting metastasis. (3) An intricate crosstalk exists between brain cancer cells and nerves. While brain cancer cell-derived factors such as Glypican-3, Neurotrophins and TSP-1 promote neurogenesis and thereby cancer proliferation, nerves release paracrine factors such as NLGN3, BDNF and IGF1 which promote the proliferation of brain cancer cells. (4) Brain cancer can also utilize the GABA neurotransmitter released by presynaptic neurons and uptake GABA by overexpressing GABAA-receptors. GABA taken up by cancer cells can be metabolized to promote brain cancer proliferation and metastasis. (Abbreviations: GluT- Glucose transporters; NLGN3- neuroligin 3; BDNF- Brain-Derived Neurotrophic Factor; IGF1- Insulin-like growth factor 1; Gln- Glutamine; VGLUT- vesicular glutamate transporters; Glu-Glutamate; GAD- glutamic acid decarboxylase; GABA-T-GABA transaminase; GAT1- GABA transporter 1; TSP-1- Thrombospondin-1; SSA- Succinic semialdehyde) (Created with BioRender)