Target AGPS To Impair Tumor Formation

· TGI - Cancer, TGI - Health, Uncategorized
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A new study by researchers at the University of California, Berkeley suggests the importance of lipids, a group of molecules that includes fatty acids and cholesterol, in the development of cancer. Study suggests that “Knocking out a single enzyme dramatically cripples the ability of aggressive cancer cells to spread and grow tumors“, offering a promising new target in the development of cancer treatments.

In the study, Nomura, principal investigator Daniel Nomura, assistant professor in UC Berkeley’s Department of Nutritional Sciences and Toxicology,  and his team tested the effects of reducing ether lipids on human skin cancer cells and primary breast tumors. They targeted an enzyme, alkylglycerone phosphate synthase, or AGPS, known to be critical to the formation of ether lipids.

The researchers first confirmed that AGPS expression increased when normal cells turned cancerous. They then found that inactivating AGPS substantially reduced the aggressiveness of the cancer cells. “The cancer cells were less able to move and invade,” said Nomura.

The researchers also 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.”

The researchers determined that inhibiting AGPS expression depleted the cancer cells of ether lipids. They also found that AGPS altered levels of other types of lipids important to the ability of the cancer cells to survive and spread, including prostaglandins and acyl phospholipids.

“This study sheds considerable light on the important role that AGPS plays in ether lipid metabolism in cancer cells, and it suggests that inhibitors of this enzyme could impair tumor formation,” said Benjamin Cravatt, professor and chair of chemical physiology at The Scripps Research Institute, who is not part of the UC Berkeley study. Cravatt is an expert in the role enzymes play in human diseases.

Study was published in the journal Proceedings of the National Academy of Sciences

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