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Study reveals new metabolic safeguards against tumor cells
Date:8/19/2009

BOSTON, Mass. (August 19, 2009) Cells don't like to be alone. In the early stages of tumor formation, a cell might be pushed out of its normal home environment due to excessive growth. But a cell normally responds to this homeless state by dismantling its nucleus, packing up its DNA, and offering itself to be eaten by immune system cells. Simply put, the homeless cell kills itself. This process, known as apoptosis, typically stops potential cancer cells before they have a chance to proliferate.

Now, researchers from the lab of Harvard Medical School professor of cell biology Joan Brugge have uncovered another mechanism that kills these precancerous, homeless cells. By studying two different types of human breast epithelial cells, the researchers found that when separated from their natural environment, these cells lose their ability to harvest energy from their surroundings. Eventually, they starve.

"We originally thought that in order for cells to survive outside their normal environment, they would simply need to suppress apoptosis," says Brugge, senior author on the paper, which will appear August 19 online in Nature. "But our studies indicate that this activity is not sufficient to prevent the demise of homeless cells. Even if they escape apoptosis, these cells can't transport enough glucose to sustain an energy supply."

Surprisingly, metabolic function is restored if antioxidant activity is increased inside the cells, allowing the cells to use energy pathways that don't rely on glucose.

"It raises the interesting idea that antioxidants, which are typically thought to be protective because they prevent genomic damage, might be allowing these potentially dangerous cells to survive," says first author Zachary Schafer, assistant professor at the University of Notre Dame and a former postdoc in Professor Brugge's lab.

The authors caution against extrapolating too far from their data, which were based on experiment
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Contact: David Cameron
david_cameron@hms.harvard.edu
617-432-0441
Harvard Medical School
Source:Eurekalert

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