Researchers in Sask., U.S. discover how one protein could unlock better cancer treatments

University of Saskatchewan professor Oleg Dmitriev and his team of researchers have identified a cell protein that could lead to more effective and less onerous cancer treatments

A team of researchers from universities in Saskatchewan, Wisconsin and Oregon have made a significant breakthrough that could improve cancer treatments in the future.

Oleg Dmitriev is a professor in the department of Biochemistry, Microbiology and Immunology at the University of Saskatchewan. He says his lab focuses on the regulation of copper and iron inside the cell.

While iron is essential in helping blood carry oxygen throughout the body, among other roles, Dmitriev says iron and copper have a dark side.

“In their free form, they can produce reactive oxygen species,” said Dmitriev. “And these are really highly damaging small molecules that indiscriminately strike everything in their path inside the cell, eventually causing cell death. And so that means that, flow of iron and copper in the cell has to be tightly regulated.”

Dmitriev says cancer cells depend on iron for their rapid growth, making it a good target for research.

“The question then becomes, can you try to disrupt iron metabolism, iron distribution and flow in the cell to unleash this destructive power of iron atoms to selectively kill cancer cells?”

The team found that one specific cell protein marker with the catchy moniker of mediator of ERBB2-driven cell motility 1, or MEMO1, binds iron and regulates the flow in and out of the cell. MEMO1 also appears at high levels in lung and prostate cancer samples, but highest in triple negative breast cancer cells.

“This is a type of cancer that is extremely difficult to treat, so that was very interesting from the medical point of view,” said Dmitriev.

“Also in lung cancer, which is a high mortality cancer. So potentially a medically very important area. And also prostate cancer. So three types of cancer where it is produced at very high level.”

Using the Canadian Light Source, researchers were able to map the protein at an atomic level.

“We used CLS to solve high resolution structures, which is in other words, [to] get a molecular snapshot that shows you exactly what that protein looks like at an atomic level, and where exactly iron or copper bind to the protein,” said Dmitriev.

By mapping the cell protein MEMO1, Dmitriev hopes new drugs can be created that target it.

“You can certainly use the structure of this protein to fit pieces in the puzzle, to look at small molecules that would exactly fit into the structure of this protein, and then make it unable to participate in the interactions with other proteins, for instance,” he said.

“But, we can also target other unrelated proteins that are only needed when MEMO1 is produced at high level in cancer cells. That would be very specific because it will leave normal cells alone, but it will hit cancer cells that have really high levels of MEMO1.”

The Canadian Cancer Society says 2 in 5 Canadians will be diagnosed with cancer in their lifetime, and 1 in 4 will die of it. Current treatments can be effective, but they are highly toxic and leave the patient with negative side effects.

Dmitriev hopes that by targeting MEMO1, new cancer treatments can be created that have less harmful reactions.

“We can then use those anti-cancer drugs at much lower doses, so that they would still kill cancer cells, but they would not affect healthy cells that much.”

The article was published in the online journal Elife in May.

Dmitriev says continued research on this subject will evaluate the role of copper in the MEMO1 protein.