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TCA cycle metabolomics of H3K27M cells grown in regular glutamine media, glutamine free media, and glutamine free media with alpha-ketoglutarate (Part-II)

ABSTRACT: Testing TCA concentrations of Diffuse Intrinsic Pontine Gliomas (DIPG) cellines with H3K27M mutations. Preliminary studies show H3K27M tumor cells are addicted to Gln for survival. Removal of Gln from media resulted in tumor cell death which was rescued by the addition of α-KG. These data show that Gln is taken up and metabolized by H3K27M tumor cells and that Gln derived α-KG is critical for the survival of these tumors. Interestingly, tumor cell death with Gln deprivation was similar to the effect of the JMJD3 inhibitor GSKJ4. Therefore, Gln derived α-KG may be required for both anaplerosis and to drive JMJD3 demethylation. We hypothesize that H3K27M tumors are reliant on α-KG that is derived from Gln to drive the TCA cycle and further decrease H3K27 methylation levels. Furthermore, inhibition of Gln metabolism may represent a novel therapeutic approach for tumors with this mutation. In this study, TCA cycle metabolomics are analyzed of H3K27M cells grown in regular glutamine media, glutamine free media, and glutamine free media with alpha-ketoglutarate.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Glioma Cells

DISEASE(S): Cancer

SUBMITTER: David Daniels

PROVIDER: ST001024 | MetabolomicsWorkbench | Wed Jul 18 00:00:00 BST 2018

REPOSITORIES: MetabolomicsWorkbench

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TCA cycle metabolomics of H3K27M cells grown in regular glutamine media, glutamine free media, and glutamine free media with alpha-ketoglutarate (Part-II)

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