Slanted Science

Cancer begins when a single cell’s DNA acquires sufficient mutations in key areas (or ‘genes‘) that it can no longer regulate its own growth. The cell begins to divide and divide repeatedly, being unable to either sense or act upon the signals coming from nearby cells telling it to “be a good neighbor and quit with all the mitosis already“. The result, perhaps only detected after several years of growth, is a tumor.

But why are some cancers relatively benign – growing in mass but showing no inclination to leave their location – while others are extremely aggressive, throwing out their seeds to grow as copies of the original cancer (or ‘metastases“) in different parts of the body? Well, scientists are reporting that they have discovered a new reason which partly explains the aggressive behavior: cancer cells can dramatically ramp up production of a protein which helps them to release energy and cellular building blocks from stored fat.

It was already known that aggressive tumor cells develop specific metabolic characteristics, which enable them to thrive in the kinds of toxic environments which exist within a cancer’s bulk. As this study notes:

Tumor cells display progressive changes in metabolism that correlate with malignancy, including development of a lipogenic phenotype.

What this study shows is that a single enzyme underlies these metabolic changes.

The enzyme is called monoacylglycerol lipase, or MAGL. The researchers, who are based at Scripps Research Institute in California and are led by Benjamin Cravatt, noticed that the enzyme was present at much higher levels in tumors which were clinically the most aggressive.

Interestingly, they saw that MAGL overexpression was leading to the breakdown of cells’ fat molecules into their component subunits, such as fatty acids. This is not a property associated with MAGL in normal tissues. These free fatty acids can then be recycled to produce new cells and also to actively promote a tumor’s growth.

Or, as the authors so neatly put it:

MAGL is highly expressed in aggressive human cancer cells and primary tumors, where it regulates a fatty acid network enriched in oncogenic signaling lipids that promotes migration, invasion, survival, and in vivo tumor growth.

By genetic manipulation of laboratory cancer models, they show that non-aggressive tumors can be made to act aggressively merely by switching on expression of MAGL. More pertinently for humans, when exposed to a drug which inhibits the activity of MAGL, aggressive tumors behave more passively.

The authors hint at possible reasons for the associaiton between obesity and cancer incidence:

We have shown that cancer cells have their own pathways to produce free fatty acids, which will enable them to become more aggressive. 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.

If you’d like to read the paper in full, you can download it from here.  Also, two of the authors have posted a really nice discussion of their work on YouTube. Here it is:

Don’t Hold Your Breath, But This May Lead To: the obvious big target for this research would be seeing a drug get into the clinic which can disrupt the activity of MAGL, thus reducing a tumor’s aggressive behavior. In the meantime: we’re off to the gym.