Glucose2

Researchers are hopeful that the enzyme PKM2 (pyruvate kinase M2), which governs a cell’s use of glucose, may be a good drug target, because both inhibiting it or activating it can slow down cancer cell growth, says Jing Chen. Above, a model of the glucose molecule. Cancer cells tend to use more glucose than normal cells. (Courtesy: Wikimedia Commons)

EMORY (US)—Cancer cells tend to consume more blood sugar than healthy cells and scientists have discovered a way to possibly exploit that craving for glucose.

Cancer cells often outgrow their blood supply, leading to a lack of oxygen in a tumor, says Jing Chen, assistant professor of hematology and medical oncology at Emory University School of Medicine and Winship Cancer Institute.

Normally cells have two modes of burning glucose—comparable to sprinting and long-distance running: glycolysis, which doesn’t require oxygen and doesn’t consume all of the glucose molecule, and oxidative phosphorylation, which requires oxygen and is more thorough.

“Even if they have oxygen, cancer cells still prefer glycolysis,” Chen says. “They depend on it to grow quickly.”

Working with Chen, postdoctoral researcher Taro Hitosugi focused on the enzyme PKM2 (pyruvate kinase M2), which governs the use of glucose and controls whether cells make the switch between glycolysis and oxidative phosphorylation.

PKM2 is found predominantly in fetal and tumor cells.

In many types of cancer, mutations lead to over-activation of proteins called tyrosine kinases. Chen’s team showed that tyrosine kinases turn off PKM2 in lung, breast, prostate, and blood cancers.

The team found that by introducing a form of PKM2 that is not sensitive to tyrosine kinases into cancer cells, they were forced to grow slower and be more dependent on oxygen.

Because the active form of PKM2 consists of four protein molecules stuck together, having a tyrosine kinase flip the “off” switch on one molecule can dampen the activity for the others.

“People knew that tyrosine kinases might modify PKM2 for decades but they didn’t think it mattered,” Chen says.

“We showed that such a modification is important and you even don’t need that much modification of PKM2 to make a difference in the cells’ metabolism.”

PKM2 could be a good drug target, because both inhibiting it or activating it can slow down cancer cell growth, Chen says. Biotechnology companies are already searching for ways to do so.

Scientists from Dana Farber Cancer Institute, Yale University, Cell Signaling Technology, and Novartis contributed to the paper, which was published in the journal Science Signaling.

The research was supported by the National Institutes of Health, the American Cancer Society, and the Multiple Myeloma Research Foundation.

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