Matches in SemOpenAlex for { <https://semopenalex.org/work/W2887986136> ?p ?o ?g. }
Showing items 1 to 73 of
73
with 100 items per page.
- W2887986136 abstract "The GABA (γ-aminobutyric acid) shunt, a bypass mechanism for a portion of the tricarboxylic acid (TCA) cycle, is responsible in the mammalian central nervous system for the synthesis and degradation of the inhibitory neurotransmitter GABA. Glutamic acid decarboxylase (GAD67 and GAD65; gene names GAD1 and GAD2, respectively) synthesizes GABA from glutamate, while GABA-transaminase (GABA-T; gene name ABAT) metabolizes GABA into succinic semialdehyde, which is dehydrogenated into succinate. Although poorly studied in mammals, the GABA shunt plays a protective role against pH, thermo-, and oxidative stresses in plants and bacteria. We hypothesize that both cell non-autonomous GABA from the tumor microenvironment (TME), and cell-autonomous production of GABA contribute to cancer progression. Cell types within the TME such as endothelial and T-cells, are known to secrete GABA. To investigate the utilization of cell non-autonomous GABA by prostate cancer cells, we determined via LC-MS/MS that although the prostate adenocarcinoma LNCaP cell line does not contain significant amounts of GABA, it is capable of taking up exogenous GABA. The effect of exogenous GABA treatment on the metabolic capacity of LNCaP cells was examined using the SEAhorse XF24 Bioanalyzer. GABA treatment increased oxygen consumption rate while decreasing the rate of glycolysis and glycolytic reserve. This effect was blocked by co-treatment with GABA-T inhibitors, suggesting the ability of GABA to increase mitochondrial respiration occurs through the GABA shunt. GABA treatment did not affect the metabolic phenotype of a normal epithelial cell line control. Regarding cell-autonomous production of GABA, recent studies show dysregulation of genes encoding GABA shunt enzymes in various cancers; specifically relevant to this study, GAD1 is upregulated in castration-resistant prostate cancer cell lines (Ippolito 2014). Consistent with the involvement of GAD1 in aggressive prostate cancers, our analysis of the TCGA Provisional prostate cancer dataset reveals that GAD1 mRNA expression level increases with increasing Gleason Score (Pearson r = 0.19; p Citation Format: Erika L. Knott, Sumitra Miriyala, Hyung Nam, Manikandan Panchatcharam, Nancy Leidenheimer. The role of the GABA shunt in prostate cancer metabolic reprogramming and aggressive phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5486." @default.
- W2887986136 created "2018-08-22" @default.
- W2887986136 creator A5000459581 @default.
- W2887986136 creator A5023897671 @default.
- W2887986136 creator A5037625892 @default.
- W2887986136 creator A5048216150 @default.
- W2887986136 creator A5055938669 @default.
- W2887986136 date "2018-07-01" @default.
- W2887986136 modified "2023-10-14" @default.
- W2887986136 title "Abstract 5486: The role of the GABA shunt in prostate cancer metabolic reprogramming and aggressive phenotype" @default.
- W2887986136 doi "https://doi.org/10.1158/1538-7445.am2018-5486" @default.
- W2887986136 hasPublicationYear "2018" @default.
- W2887986136 type Work @default.
- W2887986136 sameAs 2887986136 @default.
- W2887986136 citedByCount "1" @default.
- W2887986136 countsByYear W28879861362018 @default.
- W2887986136 crossrefType "proceedings-article" @default.
- W2887986136 hasAuthorship W2887986136A5000459581 @default.
- W2887986136 hasAuthorship W2887986136A5023897671 @default.
- W2887986136 hasAuthorship W2887986136A5037625892 @default.
- W2887986136 hasAuthorship W2887986136A5048216150 @default.
- W2887986136 hasAuthorship W2887986136A5055938669 @default.
- W2887986136 hasConcept C121608353 @default.
- W2887986136 hasConcept C165135838 @default.
- W2887986136 hasConcept C170493617 @default.
- W2887986136 hasConcept C181199279 @default.
- W2887986136 hasConcept C185592680 @default.
- W2887986136 hasConcept C20251656 @default.
- W2887986136 hasConcept C2776107976 @default.
- W2887986136 hasConcept C2777771985 @default.
- W2887986136 hasConcept C2779723316 @default.
- W2887986136 hasConcept C54355233 @default.
- W2887986136 hasConcept C55493867 @default.
- W2887986136 hasConcept C61174792 @default.
- W2887986136 hasConcept C62231903 @default.
- W2887986136 hasConcept C86803240 @default.
- W2887986136 hasConcept C9497952 @default.
- W2887986136 hasConcept C95444343 @default.
- W2887986136 hasConcept C96232424 @default.
- W2887986136 hasConceptScore W2887986136C121608353 @default.
- W2887986136 hasConceptScore W2887986136C165135838 @default.
- W2887986136 hasConceptScore W2887986136C170493617 @default.
- W2887986136 hasConceptScore W2887986136C181199279 @default.
- W2887986136 hasConceptScore W2887986136C185592680 @default.
- W2887986136 hasConceptScore W2887986136C20251656 @default.
- W2887986136 hasConceptScore W2887986136C2776107976 @default.
- W2887986136 hasConceptScore W2887986136C2777771985 @default.
- W2887986136 hasConceptScore W2887986136C2779723316 @default.
- W2887986136 hasConceptScore W2887986136C54355233 @default.
- W2887986136 hasConceptScore W2887986136C55493867 @default.
- W2887986136 hasConceptScore W2887986136C61174792 @default.
- W2887986136 hasConceptScore W2887986136C62231903 @default.
- W2887986136 hasConceptScore W2887986136C86803240 @default.
- W2887986136 hasConceptScore W2887986136C9497952 @default.
- W2887986136 hasConceptScore W2887986136C95444343 @default.
- W2887986136 hasConceptScore W2887986136C96232424 @default.
- W2887986136 hasLocation W28879861361 @default.
- W2887986136 hasOpenAccess W2887986136 @default.
- W2887986136 hasPrimaryLocation W28879861361 @default.
- W2887986136 hasRelatedWork W1973036546 @default.
- W2887986136 hasRelatedWork W1978212802 @default.
- W2887986136 hasRelatedWork W1979511946 @default.
- W2887986136 hasRelatedWork W2070985058 @default.
- W2887986136 hasRelatedWork W2258751462 @default.
- W2887986136 hasRelatedWork W2415740112 @default.
- W2887986136 hasRelatedWork W276153767 @default.
- W2887986136 hasRelatedWork W2887986136 @default.
- W2887986136 hasRelatedWork W4210773029 @default.
- W2887986136 hasRelatedWork W952479862 @default.
- W2887986136 isParatext "false" @default.
- W2887986136 isRetracted "false" @default.
- W2887986136 magId "2887986136" @default.
- W2887986136 workType "article" @default.