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University of Utah biochemists have made a breakthrough in understanding how cancer cells feed on glucose, possibly paving the way for new drugs designed to starve cancer into submission.
Cancer cells use glucose in tandem with another crucial nutrient, the protein glutamine, an amino acid found in many foods, according to findings published this week by researchers at the Huntsman Cancer Institute. The findings could spur development of new chemotherapies that would stall tumor growth by deactivating cancer cells' ability to use glucose, said Don Ayer, a professor of oncological sciences whose lab published the research in the Proceedings of the National Academy of Science .
For decades, science has known that cancer cells suck up inordinate quantities of glucose, nature's ubiquitous biological fuel, in a process that quickly blows tiny tumors into deadly malignancies.
PET scans use cancer cells' high rate of glucose metabolism to build images of tumors. These cells also need glutamine, just like normal cells.
"It's absolutely clear you need both for tumor growth. They seem to need it more than other nutrients. If you deprive them of one or the other, tumors don't grow," Ayer said.
Mohan Kaadige, a postdoctoral researcher in Ayer's lab, spearheaded the study, whose co-authors include Ayer; Sadhaasivam Kamalanaadhan, also a member of the Ayer lab; and Ryan Looper, an assistant professor in the Department of Chemistry. The lab's work, funded by the National Institutes of Health and the American Cancer Society, seeks to unlock the molecular mysteries associated with tumor proliferation.
"Research into the factors that regulate the metabolism and growth of cancer cells is still at an early stage," said Janet Shaw, a U. professor in the Department of Biochemistry and a former Huntsman researcher. "Dr. Ayer's discovery that glutamine and glucose utilization are linked is important because it identifies a number of new molecular targets that could be manipulated to interfere with the growth and survival of tumor cells."
This week's discovery builds on the lab's previous research identifying the role of MondoA, a protein that switches genes on and off, in tumorigenesis. This protein affects the gene TXNIP, which suppresses tumor growth by blocking glucose uptake into cancer cells. The Ayer team discovered that in the presence of glutamine, MondoA deactivates TXNIP. This is important because it suggests new ways to impede tumor growth.
"If you don't have glutamine, the cell is short-circuited due to a lack of glucose, which halts the growth of the tumor cell," Ayer said.
The next step is to learn how the Mondo protein works in relationship with glutamine.
"If you can modify the metabolism of the tumor cell you can have a benefit. This is not a new idea," Ayer said. "If we can figure out how glutamine signals to Mondo, that has quite a bit of chemotherapeutic potential."
Were it developed, a drug that blocks glucose uptake would not likely choke off normal cell growth, as many cancer chemotherapy drugs currently do because of their toxicity.
"Tumor cells seem to be addicted to glucose. Normal cells are not. They grow at a slower rate and if you challenge them with nutrient deprivation they can be more flexible," Ayer said.
Ayer emphasized that his lab's findings shed no light on dietary impacts on tumor growth. Glutamine is the most common amino acid in our bodies and glucose levels are tightly regulated by our endocrine system, regardless of sugar consumption.
The fact that cancer cells might die if deprived of glucose doesn't mean cancer patients should cut sugar out of their diets, researchers say.
Cancer patients should eat a balanced diet to promote good health. Cutting out sugar would not inhibit tumor growth, said Don Ayer, a professor of oncological sciences at the Huntsman Cancer Institute. Even with a sugar-free diet, there still would be plenty of glucose in the blood to feed cancer.