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Switching breast cancer off

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Switching breast cancer off

key regulators of cell signaling pathways – are commonly implicated in the proliferation of malignant tumors. The EPHA2 RTK is overexpressed in aggressive forms of breast cancer, and this overexpression correlates with poor patient outcomes.

EPHA2 is believed to operate somewhat like a switch: when its ligand, ephrin-A1, is present, EPHA2 can suppress tumor proliferation. When ephrin-A1 is absent, EPHA2 can promote tumor malignancy. However, the exact role of ephrin-A1 in tumor suppression was unknown.

Now, in the April 1 issue of Cancer Research, Jin Chen, M.D., Ph.D., Dana Brantley-Sieders, Ph.D., and colleagues showed that loss of ephrin-A1 enhances glutaminolysis – a metabolic pathway that results in lipid accumulation and tumor growth. They found that pharmacologically inhibiting glutaminolysis reversed the effects of knocking down ephrin-A1 expression.

The findings link EPHA2 signaling to glutamine metabolism and suggest new therapeutic targets for cancer subtypes that use glutamine to fuel their growth.

source : Vanderbilt University

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