| Title |
A driver role for GABA metabolism in controlling stem and proliferative cell state through GHB production in glioma
|
|---|---|
| Published in |
Acta Neuropathologica, December 2016
|
| DOI | 10.1007/s00401-016-1659-5 |
| Pubmed ID | |
| Authors |
Elias A. El-Habr, Luiz G. Dubois, Fanny Burel-Vandenbos, Alexandra Bogeas, Joanna Lipecka, Laurent Turchi, François-Xavier Lejeune, Paulo Lucas Cerqueira Coehlo, Tomohiro Yamaki, Bryan M. Wittmann, Mohamed Fareh, Emna Mahfoudhi, Maxime Janin, Ashwin Narayanan, Ghislaine Morvan-Dubois, Charlotte Schmitt, Maité Verreault, Lisa Oliver, Ariane Sharif, Johan Pallud, Bertrand Devaux, Stéphanie Puget, Penelope Korkolopoulou, Pascale Varlet, Chris Ottolenghi, Isabelle Plo, Vivaldo Moura-Neto, Thierry Virolle, Hervé Chneiweiss, Marie-Pierre Junier |
| Abstract |
Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4-hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation. Enhancing GHB levels via SSADH downregulation or GHB supplementation triggered cell conversion into a less aggressive phenotypic state. GHB affected adult glioblastoma cells with varying molecular profiles, along with cells from pediatric pontine gliomas. In all cell types, GHB acted by inhibiting α-ketoglutarate-dependent Ten-eleven Translocations (TET) activity, resulting in decreased levels of the 5-hydroxymethylcytosine epigenetic mark. In patients, low SSADH expression was correlated with high GHB/α-ketoglutarate ratios, and distinguished weakly proliferative/differentiated glioblastoma territories from proliferative/non-differentiated territories. Our findings support an active participation of metabolic variations in the genesis of tumor heterogeneity. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 3 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 2 | 67% |
| Members of the public | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 108 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 108 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 22 | 20% |
| Student > Bachelor | 14 | 13% |
| Student > Ph. D. Student | 11 | 10% |
| Other | 8 | 7% |
| Student > Master | 7 | 6% |
| Other | 19 | 18% |
| Unknown | 27 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 22 | 20% |
| Medicine and Dentistry | 20 | 19% |
| Agricultural and Biological Sciences | 9 | 8% |
| Neuroscience | 7 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 4% |
| Other | 6 | 6% |
| Unknown | 40 | 37% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 April 2022.
All research outputs
#6,812,267
of 24,716,872 outputs
Outputs from Acta Neuropathologica
#1,370
of 2,510 outputs
Outputs of similar age
#119,298
of 431,185 outputs
Outputs of similar age from Acta Neuropathologica
#24
of 34 outputs
Altmetric has tracked 24,716,872 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 2,510 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 16.3. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
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We're also able to compare this research output to 34 others from the same source and published within six weeks on either side of this one. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.