MAGL was known to break down stored fats, but had never been shown to regulate free fatty acid production. "So this told us that it is an acquired activity of aggressive cancer cells," says Nomura. "As cancer cells become more aggressive, the lipase is increased and its activity is targeted to the release of free fatty acid." In other words, cancer cells co-opted MAGL's activity to support their progression.

Explaining the Link to Obesity

The finding that MAGL regulates the production of free fatty acids in aggressive cancer cells provides a possible explanation for the reported link between obesity and cancer.

People who eat foods high in fats are constantly introducing free fatty acids in their bodies. "We have shown that cancer cells have their own pathways to produce free fatty acids, which will enable them to become more aggressive," says Cravatt. "Less malignant cancer cells do not appear to have yet adopted an autonomous pathway to increase their own pools of free fatty acids. Thus, taking free fatty acids from the diet could assist these cells in developing a more malignant phenotype."

Many more experiments are needed to evaluate whether blocking MAGL's activity might serve to curb cancer's progression in people, which could offer a new type of cancer therapy. Because the enzyme is not needed for cell survival-rather for progression to more aggressive behaviors-it may offer some advantages over existing therapies.

"It might have a better safety profile because it does not target a general survival mechanism common to all cells," explains Cravatt.

Source: Scripps Research Institute