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Understanding cancer energetics
Date:6/3/2011

for the ride, showing that the two proteins do in fact bind to each other.

Knowing that the primary function of HIF-1 is to bind DNA and turn on specific genes, Semenza's team next asked whether PKM2 somehow helped HIF-1 do that. They examined genes known to be activated by HIF-1 in low oxygen after the removal of PKM2 and found that without PKM2, less HIF-1 was bound to DNA.

Now armed with evidence that PKM2 helps HIF-1 turn on genes, the team looked at the activity of genes directly involved in the metabolic pathway that burns so much sugar in cancer cells and compared genes known to be activated by HIF-1 with those not affected by HIF-1. Removing PKM2 from cells had no effect on genes not controlled by HIF-1 but reduced the activity of HIF-1-controlled genes.

"These results were really astounding," says Semenza. "In addition to solving the long-standing mystery of the Warburg effect, we also discovered that PKM2 may play a far broader role in promoting cancer progression than has been appreciated before."


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Contact: Audrey Huang
audrey@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
Source:Eurekalert

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