@article{84d7e7dfcaa944d5aff86e41e7a3b5ed,
title = "Electrical and synaptic integration of glioma into neural circuits",
abstract = "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.",
author = "Venkatesh, {Humsa S.} and Wade Morishita and Geraghty, {Anna C.} and Dana Silverbush and Gillespie, {Shawn M.} and Marlene Arzt and Tam, {Lydia T.} and Cedric Espenel and Anitha Ponnuswami and Lijun Ni and Woo, {Pamelyn J.} and Taylor, {Kathryn R.} and Amit Agarwal and Aviv Regev and David Brang and Hannes Vogel and Shawn Hervey-Jumper and Bergles, {Dwight E.} and Suv{\`a}, {Mario L.} and Malenka, {Robert C.} and Michelle Monje",
note = "Funding Information: Acknowledgements We gratefully acknowledge support from the National Institutes of Health (NIH) Director{\textquoteright}s Common Fund (DP1 NS111132 to M.M.), National Institute of Neurological Disorders and Stroke (R01 NS092597 to M.M., K08 NS110919 to S.H.-J.), National Cancer Institute (F31 CA200273 to H.S.V.), National Institutes of Mental Health (P50 MH086403 to R.C.M.), Michael Mosier Defeat DIPG Foundation (to M.M.), ChadTough Foundation (to M.M.), V Foundation (to M.M.), Department of Defense (NF140075 to M.M.), McKenna Claire Foundation (to M.M.), Alex{\textquoteright}s Lemonade Stand Foundation (to M.M.), The Cure Starts Now Foundation and DIPG Collaborative (to M.M.), Unravel Pediatric Cancer (to M.M.), N8 Foundation (to M.M.), Abbie{\textquoteright}s Army Foundation (to M.M.), Brantley{\textquoteright}s Project supported by Ian{\textquoteright}s Friends Foundation (to M.M.), Waxman Family Research Fund (to M.M.), Joey Fabus Childhood Cancer Foundation (to M.M.), Virginia and D.K. Ludwig Fund for Cancer Research (to M.M.), Bio-X Institute (to L.T.T. and A.C.G.), Maternal and Child Health Research Institute at Stanford (to M.M., A.C.G and H.S.V.), Anne T. and Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer and Blood Diseases (to M.M.), Cancer Research UK (to M.M.), Dr. Mildred Scheel Cancer Foundation (57406718 to M.A.), Damon Runyan Foundation (to K.R.T.), Sontag Foundation Distinguished Scientist Award (to M.L.S.), Howard Hughes Medical Institute (to A.R.), Klarman Cell Observatory (to A.R.), Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to D.E.B.), Chica and Heinz Schaller Research Foundation (to A.A.), Deutsche Forschungsgemeinschaft (AG 287/1-1 to A.A.), The Robert Wood Johnson Foundation (74259 RWJF to S.H.-J.). We thank S. Knemeyer for illustrations, and A. Olsen, S. Kakaizada and M. Shore for technical assistance. Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2019",
month = sep,
day = "26",
doi = "10.1038/s41586-019-1563-y",
language = "English (US)",
volume = "573",
pages = "539--545",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7775",
}