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Study identifies an expanded role for PKM2 in helping cancer cells survive
Date:11/3/2011

BOSTON It has long been known that cancer cells use nutrients differently than normal cells. In recent years, the rapidly reemerging field of cancer metabolism has shed new light on the ways that cancers use glucose to grow and thrive, demonstrating that manipulation of an enzyme called PKM2 is important to this metabolic process.

Now a new study led by a scientific team at Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS) has uncovered another key mechanism that cancer cells use as part of their survival strategy -- and once again it seems that they are using PKM2 to their advantage.

Reported in the Nov. 3 express online edition of Science, the new findings show that by keeping PKM2 activity at lower-than-normal levels, cancer cells are able to withstand damage caused by oxidative stress and the generation of potentially toxic reactive oxygen species (ROS). Importantly, the study shows that small-molecule PKM2 activator drugs could be a way to interfere with this process and thereby disrupt tumor growth .

"Many cancer cells take up glucose at higher rates than most normal cells, and then use the sugar in a distinct way to fuel their proliferation," explains senior author Lewis Cantley, PhD, Director of the Cancer Center at BIDMC and the William Bosworth Castle Professor of Medicine at HMS. "Several years ago, it was discovered that the M2 form of the pyruvate kinase enzyme [PKM2] plays a key role in this metabolic process. Now, these new findings demonstrate yet another way that cancer cells are able to manipulate PKM2 to their advantage, suggesting that by keeping PKM2 activity low, cancer cells channel incoming glucose to metabolic pathways that generate antioxidants, and thereby survive oxidative stress."

Glycolysis is a multi-step process in which glucose is broken down so that cells can make use of the sugar for energy and other essential functions, and the PKM2 enzyme is resp
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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