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The mystery enzyme: how cancer cells feed off sugar

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Back in the 1920s, Dr Warburg, a physiologist, discovered that cancer cells need glucose – the sugar in our blood – to thrive and grow. It’s their primary energy source, and yet they choose an extremely inefficient way of getting that energy.

Healthy cells use the mitochondria, the energy-producing structures within cells, to produce ATP (adenosine triphosphate), which drives most of our functions. But cancer cells are different; they change their metabolism, and cease to rely on oxygen, in order to ferment sugar in what became known as the Warburg effect.

“This has been a mystery for quite some time. Why would cancer cells, which need large amounts of energy to sustain their growth, prefer to use a pathway that produces less ATP than another available pathway?” asked Prof Bert O’Malley from Baylor College of Medicine.

Years ago, O’Malley and his team discovered that cancer cells over-produce the protein SRC-3, and this allows them to turn on genes that cause abnormal growth and metastasis (growth), characteristics of cancer.

So what makes a cancer cell produce more SRC-3? The unsuspected culprit is an enzyme known as PFKFB4, and this turns SRC-3s into potent drivers of most cancers, and especially breast cancer.

This opens the door to new cancer therapies. Just remove either the PFKFB4s or the SRC-3s from cancer cells, and you stop it in its tracks. Cancer stops growing and it can’t come back.

(Source: Nature, 2018; doi: 10.1038/s41586-018-0018-1)

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