biostudies-literatureUnknown133(4)El-Habr EACell 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, alongActa neuropathologica645-660https://www.ebi.ac.uk/biostudies/studies/S-EPMC5348560biostudies-literatureA driver role for GABA metabolism in controlling stem and proliferative cell state through GHB production in glioma.PMC5348560Yamaki TKorkolopoulou PPallud JDubois LGNarayanan AVerreault MWittmann BMCoehlo PLLejeune FXMorvan-Dubois GOttolenghi CJanin MDevaux BMoura-Neto VJunier MPSharif AVirolle TPlo IBurel-Vandenbos FVarlet PPuget SEl-Habr EALipecka JTurchi LFareh MOliver LChneiweiss HMahfoudhi ESchmitt CBogeas AfalseA driver role for GABA metabolism in controlling stem and proliferative cell state through GHB production in glioma.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, along2017-01-01T00:00:00Z2017 Apr2026-05-30T09:05:33.688Z2019-03-27T02:38:35ZS-EPMC53485602803221510.1007/s00401-016-1659-5