Research ArticleMetabolism

The induction of HAD-like phosphatases by multiple signaling pathways confers resistance to the metabolic inhibitor 2-deoxyglucose

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Science Signaling  03 Sep 2019:
Vol. 12, Issue 597, eaaw8000
DOI: 10.1126/scisignal.aaw8000

Resisting a metabolic poison

Once imported into cells and phosphorylated, the glucose analog 2-deoxyglucose (2DG) inhibits glycolysis, leading to the proposal of using 2DG as a cancer treatment. Using yeast as a model, Defenouillère et al. investigated how cells become resistant to 2DG. Exposure to 2DG activated several signaling pathways that resulted in the increased expression of the gene encoding the phosphatase Dog2. In contrast, glucose availability transcriptionally repressed DOG2 expression. When overexpressed, a human homolog of Dog2 conferred 2DG resistance to human cells, suggesting that cancer cells with increased abundance of this phosphatase could escape the toxic effects of 2DG.

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