The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Neuronal Activity Promotes Glioma Growth through Neuroligin-3 Secretion
Open accessAbstract
SUMMARY Active neurons exert a mitogenic effect on normal neural precursor and oligodendroglial precursor cells, the putative cellular origins of high-grade glioma (HGG). By using optogenetic control of cortical neuronal activity in a patient-derived pediatric glioblastoma xenograft model, we demonstrate that active neurons similarly promote HGG proliferation and growth in vivo. Conditioned medium from optogenetically stimulated cortical slices promoted proliferation of pediatric and adult patient-derived HGG cultures, indicating secretion of activity-regulated mitogen(s). The synaptic protein neuroligin-3 (NLGN3) was identified as the leading candidate mitogen, and soluble NLGN3 was sufficient and necessary to promote robust HGG cell proliferation. NLGN3 induced PI3K-mTOR pathway activity and feedforward expression of NLGN3 in glioma cells. NLGN3 expression levels in human HGG negatively correlated with patient overall survival. These findings indicate the important role of active neurons in the brain tumor microenvironment and identify secreted NLGN3 as an unexpected mechanism promoting neuronal activity-regulated cancer growth.
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Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
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“It is possible that NLGN3 is secreted directly from active neurons or from OPCs, which act as post-synaptic cells in axoglial synapses (Bergles et al., 2010; Bergles et al., 2000) and express the highest level of Nlgn3 mRNA of any neural cell type (Zhang et al., 2014).”
Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
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Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism
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Self-citationGlutamatergic synaptic input to glioma cells drives brain tumour progression
Venkataramani, V., Tanev, D. I., Strahle, C., Studier-Fischer, A., Fankhauser, L., Kessler, T., Körber, C., Kardorff, M., Ratliff, M., Xie, R., et al. (2019) · Nature · doi:10.1038/s41586-019-1564-x · Cited by 1,197
Identification of diverse astrocyte populations and their malignant analogs
John Lin, C.-C., Yu, K., Hatcher, A., Huang, T.-W., Lee, H. K., Carlson, J., Weston, M. C., Chen, F., Zhang, Y., Zhu, W., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4493 · Cited by 525
Metadata
- Authors
- Venkatesh, H. S., Johung, T. B., Caretti, V., Noll, A., Tang, Y., Nagaraja, S., Gibson, E. M., Mount, C. W., Polepalli, J., Mitra, S. S., Woo, P. J., Malenka, R. C., Vogel, H., Bredel, M., Mallick, P., & Monje, M.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 161
- Issue
- 4
- Pages
- 803-816
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2111940175
- Cited by
- 963
- References
- 11
- FWCI
- 21.85
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Venkatesh, H. S., Johung, T. B., Caretti, V., Noll, A., Tang, Y., Nagaraja, S., Gibson, E. M., Mount, C. W., Polepalli, J., Mitra, S. S., Woo, P. J., Malenka, R. C., Vogel, H., Bredel, M., Mallick, P., & Monje, M. (2015). Neuronal Activity Promotes Glioma Growth through Neuroligin-3 Secretion. Cell. https://doi.org/10.1016/j.cell.2015.04.012
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