Essays on Science and SocietyMOLECULAR MEDICINE

The neural regulation of cancer

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Science  22 Nov 2019:
Vol. 366, Issue 6468, pp. 965
DOI: 10.1126/science.aaz7776

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  • Neuronal activity drives cancer growth and progression through direct signaling mechanisms and the functional integration of glioma into neural circuitry. An important mechanism that mediates the neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic adhesion molecule neuroligin-3 (NLGN3), which promotes glioma proliferation through the PI3K–mammalian target of rapamycin (mTOR) pathway and induces up-regulation of several synapse-related genes. NLGN3 is cleaved through the ADAM10 sheddase. ADAM10 inhibitors prevent the release of NLGN3 into the tumor microenvironment and robustly block cancer growth. Additional neuron-glioma interactions include electrical and synaptic integration of glioma into neural circuitry through direct electrochemical synaptic transmission. Synaptic activity depolarizes electrically coupled glioma cell networks, and this depolarization in turn induces proliferation. These findings suggest that neuron-glioma circuit dynamics are integral to tumor progression. [Figure adapted from (5)]

    GRAPHIC: N. DESAI/SCIENCE FROM H. VENKATESH

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