Research ArticleCancer Metabolism

The receptor tyrosine kinase EphA2 promotes glutamine metabolism in tumors by activating the transcriptional coactivators YAP and TAZ

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Science Signaling  05 Dec 2017:
Vol. 10, Issue 508, eaan4667
DOI: 10.1126/scisignal.aan4667

EphA2 exposes an Achilles’ heel in breast cancer

Cancer cells alter their metabolism to adapt to the tumor microenvironment, for example, by switching from a reliance on glucose to glutamine. Edwards et al. found that a high abundance of the receptor tyrosine kinase EphA2 drives a switch to glutamine dependency in HER2-positive breast cancers. In cells and mouse models, EphA2 activated Rho-ROCK signaling that mediated the nuclear accumulation of the transcriptional coactivators YAP and TAZ, where they induced the expression of genes encoding an amino acid transporter that promoted glutamine uptake and an enzyme that promoted glutamine metabolism. EphA2 may be a biomarker for sensitivity to glutaminase inhibitors in patient tumors. However, because inhibiting glutamine metabolism may have adverse effects elsewhere, such as in the immune system, inhibiting EphA2 signaling upstream of YAP and TAZ may be a way to exploit the glutamine dependency of HER2-positive breast cancers.

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