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Cancer Cells Reprogram Energy Needs To Grow And Spread

Semenza and colleagues measured mitochondria content and oxygen use in kidney cancer cells that contain no VHL protein and in the same cells with VHL engineered back in. Restoring VHL caused the cells to make two to three times more mitochondria and use two to three times more oxygen.

VHL normally blocks the action of HIF-1, a protein that the Hopkins group discovered in 1992. Cells normally make HIF-1 only under low oxygen conditions, when fermentation is necessary to make energy. However, in the absence of VHL, HIF-1 is active even when oxygen is plentiful and switches on genes that help a cell take up more glucose.

This current work shows that excess HIF-1 counteracts a protein called MYC, which normally stimulates cells to make mitochondria. Because MYC is turned on in many other cancers, these results suggest that shutting down the mitochondria must be a very important event in kidney cancer, Semenza notes.

There is currently no treatment available for patients with advanced kidney cancer. Scientists at pharmaceutical companies, the National Cancer Institute, and laboratories at Hopkins and other universities are investigating whether drugs that inhibit HIF-1 may be useful for cancer therapy.


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