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MYCN upregulates the transsulfuration pathway to suppress the ferroptotic vulnerability in MYCN-amplified neuroblastoma
FIGURE 1: Overexpression of MYCN leads to high levels of cystathionine. (A) Changes in key metabolites of the glutathione and the transsulfuration pathway after analyzing SK-N-SH MYCN and GFP cells by untargeted liquid chromatography/tandem mass spectrometry. Samples were run in quintuplicate. For high throughput/untargeted metabolomics, compounds are resolved by liquid chromatography and then analyzed for mass and fragmentation by tandem mass spectrometry. In complex biological mixtures such as cell lysates, the liquid chromatography-based resolution is not optimized for any one metabolite, and therefore some metabolites of interest (e.g., cystathionine) may not be readily identified. The numbers represent the log2 (fold change) of the metabolites in SK-N-SH MYCN compared to SK-N-SH GFP cells; p-values were determined by t-test with false discovery rate. (B) DEPMAP (Broad Institute consortium) analysis of the correlation between cystathionine and MYCN expression among 910 cancer cell lines of all cancer subtypes. For all statistical considerations differences were considered statistically significant if P < 0.05. For all calculated P values: *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.