Halting Lipid-Forming Enzyme May Stop Cancer Spread
Disabling a single enzyme associated with the formation of lipids significantly disrupts the ability of aggressive cancer cells to spread and grow tumors, according to a new study.
Researchers said the latest findings provide insight into the importance of lipids, a group of molecules that includes fatty acids and cholesterol, and the development of new cancer treatments.
Cancer cells have long been known to metabolize lipids differently. Levels of ether lipids, a class of lipids that are harder to break down, are particularly elevated in highly malignant tumors. However, the nature of that correlation has been unclear for decades.
"Cancer cells make and use a lot of fat and lipids, and that makes sense because cancer cells divide and proliferate at an accelerated rate, and to do that, they need lipids, which make up the membranes of the cell," study principal investigator Daniel Nomura, assistant professor in UC Berkeley's Department of Nutritional Sciences and Toxicology, said in a news release.
"Lipids have a variety of uses for cellular structure, but what we're showing with our study is that lipids can also send signals that fuel cancer growth," Nomura explained.
The latest research involved testing the effects of reducing ether lipids on human skin cancer cells and primary breast tumors. Researchers targeted a particular enzyme called alkylglycerone phosphate synthase or AGPS. Researchers said this enzyme is critical to the formation of ether lipids.
The findings revealed that AGPS expression increased when normal cells turned cancerous. However, inactivating AGPS significantly reduced the aggressiveness of cancer cells.
"The cancer cells were less able to move and invade," Nomura explained.
Researchers also conducted another experiment where they compared the impact of disabling the AGPS enzyme in mice that had been injected with cancer cells.
"Among the mice that had the AGPS enzyme inactivated, the tumors were nonexistent," said Nomura. "The mice that did not have this enzyme disabled rapidly developed tumors."
Researchers noted that disrupting AGPS expression lowered levels of ether lipids and other types of lipids important to the ability of the cancer cells to survive and spread, like prostaglandins and acyl phospholipids.
"The effect on other lipids was unexpected and previously unknown," lead author Daniel Benjamin, doctoral student in the Nomura Research Group, said in a statement. "Other studies have investigated specific lipid signaling pathways, but what makes AGPS stand out as a treatment target is that the enzyme seems to simultaneously regulate multiple aspects of lipid metabolism important for tumor growth and malignancy."
The findings are published in the journal Proceedings of the National Academy of Sciences.