Obesity and cancer: new data
Scientists at the Scripps Research Institute (La Jolla, California), working under the leadership of Benjamin Cravatt, have found that the hyperactivity of the fat-splitting enzyme monoacylglycerollipase (MAGL) increases the aggressiveness of some malignant cells. The results of the work are published in the January issue of the journal Cell in the article "Monoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer Pathogenesis".
The authors believe that monoacylglycerol lipase is a potential target for the treatment of particularly malignant forms of cancer, as well as to prevent the progression of the disease. In addition, the findings provide a possible explanation for the proven relationship between obesity and cancer.
As a cancerous tumor grows in the body, some malignant cells acquire more aggressive characteristics, such as the ability to penetrate into the tissues surrounding the tumor and move to remote areas of the body. To identify possible stimulators of this process, scientists compared changes in the functional status of serine hydrolase enzymes that break down proteins, fats and other biological molecules in non-aggressive and aggressive cancer cells. There is evidence that enzymes of this group are involved in the development of cancer and other diseases.
To study the enzyme status, the authors used a protein activity profiling technique that allows simultaneous observation of all active cell enzymes. Using a fluorescent label that interacts exclusively with molecules with certain chemical properties, they identified enzymes of the serine hydrolase family that exhibit abnormal activity in tumor cells.
The greatest attention of scientists was attracted by the enzyme monoacylglycerollipase, whose function is to break down the fat reserves of the cell. The activity of this enzyme was significantly increased in cells of particularly aggressive tumors and remained within the normal range in non-aggressive cancer cells. The results of a series of experiments in which researchers suppressed or stimulated the activity of monoacylglycerollipase showed that this enzyme is able to increase the degree of cell malignancy.
A detailed study of the identified mechanism showed that when activated in malignant cells, monoacylglycerol lipase actively cleaves fat reserves with the formation of a large amount of free fatty acids, which are the building material for the cell membrane and signaling fat molecules that provide intercellular signals. These free fatty acids subsequently form other small molecules that stimulate the growth and progression of cancerous tumors.
The fact that monoacylglycerol lipase breaks down fat reserves has been known for a long time, but the participation of this enzyme in the regulation of the synthesis of free fatty acids turned out to be a surprise. The authors claim that this feature is characteristic exclusively for malignant cells, and the activity of the enzyme and the level of fatty acid production increase simultaneously with an increase in the aggressiveness of cancer. In other words, the tumor uses the activity of monoacylglycerol lipase to maintain its progression.
Deciphering this mechanism provides a possible explanation for the relationship between obesity and cancer. The use of fat-rich foods ensures a constant supply of free fatty acids to the body, which can contribute to the rapid malignancy of abnormal cells appearing in the body.
The activity of monoacylglycerollipase is not vital for the cell, so its blocking can theoretically be used to suppress the progression of cancer. However, before the development of such therapies, it is necessary to conduct a lot of experimental work.
Portal "Eternal youth" http://vechnayamolodost.ru Based on ScienceDaily: Cancer Cells Co-Opt Fat Metabolism Pathway to Become More Malignant.
18.01.2010