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Researchers find potential route to limiting aggressive cancers

UW-Madison researchers have found a potential route to limiting aggressive cancers.

“Cancer cells often change their nutrient utilization and energy production, so many efforts are being made to develop drug inhibitors of cancer cell metabolism to starve them,” said Wei Xu, a professor and cancer expert at the UW Carbone Cancer Center and McArdle Laboratory for Cancer Research. “We have found that inhibiting a chemical modification of a cancer-associated metabolism protein is enough to inhibit the aggressive nature of cancer cells.”

Xu’s lab studies a protein called CARM1 which is associated with worse outcomes in breast cancer patients and has been found in other types of cancer.

“CARM1 chemically modifies its target proteins to alter their function, and in doing so directly leads to the activation of several hallmarks of cancer,” she said.

In a study published earlier this week in the journal Nature Cell Biology, Xu and her fellow investigators found that CARM1 interacts with another protein involved in cell energy metabolization called PKM2, changing its function.

About 10 years ago, researchers determined that elevated levels of PKM2 were found in in cancer cells, but the connection to cancer cell aggression wasn’t clear. Now, Xu and her team have realized that PKM2 influences the shift from normal cell metabolism to out-of-control cancer cell growth.

They found that CARM1-modified PKM2 moved cells toward the cancer cell metabolism path, while cells with PKM2 that couldn’t be modified stayed on the noncancerous metabolism route.

The researchers tested the idea with a mouse model of breast cancer, using a competitor drug to keep CARM1 from modifying PKM2.

“When we block PKM2 modification by CARM1, the metabolic energy balance in cancer cells is reversed, and we see a decrease of cell growth and cell spreading potential,” Xu says. “This study, then, identifies another therapeutic target to help reverse several hallmarks of cancer.”

These hallmarks include continuous activation of growth pathways, a lack of response to signals that slow cell growth, and invasive spreading to other parts of the body.

--By Alex Moe


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