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Scripps Research scientists find cancer cells co-opt fat metabolism pathway to become more malignant
Date:1/12/2010

LA JOLLA, CAJanuary 5, 2010An enzyme that normally helps break down stored fats goes into overdrive in some cancer cells, making them more malignant, according to new findings by a team at The Scripps Research Institute.

"Historically, research has focused on the mechanisms leading to cancer formation and therapies have focused on taking out cancer cells," says Benjamin Cravatt, chair of the Scripps Research Department of Chemical Physiology and corresponding author of the study published in the January 8, 2009 issue of the journal Cell. "But here we were looking for pathways that lead to cancer aggressiveness."

The aggressiveness-promoting enzyme, called monoacylglycerol lipase (or MAGL for short), may provide a new target for treating more malignant forms cancers or for preventing cancer progression. The findings also suggest an explanation for the reported link between obesity and cancer by showing that releasing stored fats in cancer cells can push them toward more aggressive behaviors.

Homing in on a Cancer Protein

As a cancer grows inside the body, some cells take on more aggressive characteristics, such as the ability to invade local areas and to spread to other parts of the body. To identify possible drivers in this process, Daniel Nomura, a postdoc in Cravatt's lab, compared changes in the functional state of enzymes in non-aggressive cancer cells to that of aggressive ones.

"We were looking for changes in enzyme activity," explains Nomura. In particular, the researchers were focusing on a group of enzymes, called serine hydrolases, that break down proteins, fats, and other molecules in cells. "This is one of the largest known enzyme families, comprising about one percent of all proteins in a cell," says Nomura. "And these enzymes have been implicated in cancer and other diseases."

Nomura employed a technique pioneered in Cravatt's lab called activity-based protein profiling, which all
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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