Research ArticleCancer Metabolism

Oncogenic PI3K promotes methionine dependency in breast cancer cells through the cystine-glutamate antiporter xCT

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Science Signaling  19 Dec 2017:
Vol. 10, Issue 510, eaao6604
DOI: 10.1126/scisignal.aao6604

Understanding the causes of methionine dependency

Cells can use the same precursor to produce either methionine or cysteine, but can free up cysteine from cystine, an oxidized cysteine dimer with structural functions. Methionine dependency, or the inability to efficiently produce methionine, is a metabolic vulnerability that could be exploited to treat certain cancers. Examination of several breast cancer cell lines by Lien et al. revealed a correlation between methionine dependency, the presence of oncogenic mutations in PIK3CA, which encodes the lipid kinase PI3Kα, and decreased expression of SLC7A11, which encodes the cystine transporter xCT. Oncogenic PI3Kα mutants not only transcriptionally suppressed SLC7A11 expression but also inhibited the activity of xCT through AKT-mediated phosphorylation. These results highlight how mutations in the PI3K pathway result in the metabolic reprogramming of cancer cells.

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