Fig. 1 | Signal Transduction and Targeted Therapy

Fig. 1

From: Targeting metabolic/epigenetic pathways: a potential strategy for cancer therapy in diffuse intrinsic pontine gliomas

Fig. 1

Schematic model of interplay between metabolic and epigenetic pathways in H3K27M cells. Elevated α-KG from enhanced glycolysis, glutaminolysis and tricarboxylic acid cycle metabolism inhibits H3K27me3 levels in H3.3K27M mutant cells. Reduction in H3K27me3 levels promotes gene expression including Hk2, Idh1, and Glud1, which enhances glycolysis, tricarboxylic acid cycle and glutaminolysis metabolism along with increased production of α-KG, which functioned as a vital cofactor of KDM6A/6B, resulting in demethylation of H3K27. As a result, α-KG was metabolized to succinate while demethylating H3K27me3. Noteworthily, two pharmaceuticals JHU-083 (a glutamine antagonist) and WT-IDH1i13 (an IDH1 inhibitor) were therapeutic for DIPGs. Glud1 glutamate dehydrogenase 1, GDH glutamate dehydrogenase, Hk2 hexokinase 2, Idh1 isocitrate-dehydrogenase 1, α-KG alpha-ketoglutarate

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