Journal
NATURE
Volume 573, Issue 7775, Pages 539-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-019-1563-y
Keywords
-
Categories
Funding
- National Institutes of Health (NIH) Director's Common Fund [DP1 NS111132]
- National Institute of Neurological Disorders and Stroke [R01 NS092597, K08 NS110919]
- National Cancer Institute [F31 CA200273]
- National Institutes of Mental Health [P50 MH086403]
- Michael Mosier Defeat DIPG Foundation
- ChadTough Foundation
- V Foundation
- Department of Defense [NF140075]
- McKenna Claire Foundation
- Alex's Lemonade Stand Foundation
- Cure Starts Now Foundation
- DIPG Collaborative
- N8 Foundation
- Abbie's Army Foundation
- Brantley's Project - Ian's Friends Foundation
- Waxman Family Research Fund
- Joey Fabus Childhood Cancer Foundation
- Virginia and D. K. Ludwig Fund for Cancer Research
- Bio-X Institute
- Maternal and Child Health Research Institute at Stanford
- Anne T. and Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer and Blood Diseases
- Cancer Research UK
- Dr. Mildred Scheel Cancer Foundation [57406718]
- Damon Runyan Foundation
- Sontag Foundation Distinguished Scientist Award
- Howard Hughes Medical Institute
- Klarman Cell Observatory
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Chica and Heinz Schaller Research Foundation
- Deutsche Forschungsgemeinschaft [AG 287/1-1]
- Robert Wood Johnson Foundation [74259 RWJF]
- Unravel Pediatric Cancer
Ask authors/readers for more resources
High-grade gliomas are lethal brain cancers whose progression is robustly regulated by neuronal activity. Activity-regulated release of growth factors promotes glioma growth, but this alone is insufficient to explain the effect that neuronal activity exerts on glioma progression. Here we show that neuron and glioma interactions include electrochemical communication through bona fide AMPA receptor-dependent neuron-glioma synapses. Neuronal activity also evokes non-synaptic activity-dependent potassium currents that are amplified by gap junction-mediated tumour interconnections, forming an electrically coupled network. Depolarization of glioma membranes assessed by in vivo optogenetics promotes proliferation, whereas pharmacologically or genetically blocking electrochemical signalling inhibits the growth of glioma xenografts and extends mouse survival. Emphasizing the positive feedback mechanisms by which gliomas increase neuronal excitability and thus activity-regulated glioma growth, human intraoperative electrocorticography demonstrates increased cortical excitability in the glioma-infiltrated brain. Together, these findings indicate that synaptic and electrical integration into neural circuits promotes glioma progression.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available