Stored Fats Fuel Aggressive Cancer Growth

Cancer Cells Use Stored Fats to Fuel Aggressive Growth and Spread

An enzyme that is best known for breaking down stored fats in cells may be co-opted by cancer cells so that they can become more aggressive, Scripps Research Institute investigators have reported. Blocking the activity of the enzyme, MAGL, in cell lines of several aggressive cancers and in mouse models derived from the cell lines significantly tempered cell migration and tumor growth, Dr. Daniel Nomura and colleagues reported January 8 in Cell.

In the same mice in which MAGL levels were reduced, the research team found that a high-fat diet could kick start tumor growth. This latter finding, they wrote, “has provocative implications for the crosstalk between obesity and tumorigenesis.”

To conduct the study, the researchers first analyzed the expression of certain types of enzymes in cell lines of aggressive and non-aggressive melanoma, breast, and ovarian cancer. They found that MAGL levels were significantly elevated in the aggressive cell lines. They also found that when they increased MAGL levels in the non-aggressive cancer cell lines, the cancer cells became more aggressive.

MAGL promotes this aggressive posture in cancer cells, the researchers discovered, by unleashing free fatty acids (FFAs), which are integral components of cell membranes and other molecules in cells. The increased production of FFAs, in turn, stimulates the activity of a communication network of signaling lipids known to enhance the growth of tumors and movement of cancer cells. In the mice with inhibited MAGL expression fed a high-fat diet that led to increased tumor growth, the researchers noted, the tumors had significantly elevated levels of FFAs.

The study’s findings provoke “many exciting new questions,” wrote Drs. Jessica Yecies and Brendan Manning from the Harvard School of Public Health in an accompanying editorial. Among them is whether MAGL levels could “be used as a biomarker to predict the influence of dietary fats and obesity on tumor progression