PNAS: Copper is a clue to fighting cancer

For cancer cells to grow and spread around the body, they need proteins
that bind copper ions.
New research into how cancer-associated proteins bind to this metal and how they interact with other proteins opens up potential new drug targets to fight cancer
.

Human cells need small amounts of copper to carry out important biological processes
.
Studies have shown elevated levels of copper in tumor cells and serum in cancer patients, concluding that cancer cells need more copper
than healthy cells.
High levels of copper also mean more active copper-binding proteins
.

Pernilla Wittung-Stafshede, professor of chemical biology at Chalmers University of Technology in Sweden, said: "Therefore, studying these proteins is very important for understanding the development of cancer, and a deeper understanding of them can lead to new targets for treating this disease
.
"

Most cancer-related deaths are due to metastases — secondary tumors — formed in several places in the body, such as in the liver or lungs
.
A protein called Memo1 is part of
the signaling system for cancer cells to grow and spread throughout the body.
Previous studies have shown that when the Memo1 gene is inactivated in breast cancer cells, their ability to form metastasis decreases
.

A team at Chalmers wanted to take a closer look at the link between
Memo1 and copper.
In a new study published in the scientific journal Proceedings of the National Academy of Sciences, researchers tested the ability of the Memo1 protein to
bind copper ions through a series of test-tube experiments.
They found that the protein binds to copper, but only in its reduced form
.
This form of copper ion is most commonly
found in living cells.
This is an important finding because the reduced copper, although it is needed by the body, also helps in redox reactions that destroy and even kill cells
.
The researchers found that when Memo1 interacted with copper, copper's toxic redox reaction was blocked
.

"This poses a risk to tumors relying on large amounts of copper because it triggers chemical reactions
that are harmful to cancer cells.
" We believe Memo1 protects cancer cells by binding copper when needed so they can continue to survive and spread," said
Pernilla Wittung-Stafshede, one of the study's lead authors.

The researchers also found that Memo1 can form complexes
with Atox1, another copper-binding protein found in our cells.
It is a copper transporter within human cells, and the research team has previously shown that with the help of copper, Atox1 helps breast cancer cells move and form metastases
.
Overall, the findings of the new study mean that copper and copper-binding proteins could be targets for future cancer treatments
.

"We saw how copper ions metastasized between the proteins Memo1 and Atox1 in the tube, and when we looked at breast cancer cells, we found that the two proteins were spatially close
.
Based on this, we conclude that copper exchange between these proteins can occur in cancer cells as well as in test tubes, and therefore has biological significance," says
Pernilla Wittung-Stafshede.

The researchers now hope to further determine the copper ion binding site in Memo1 and how the presence of copper affects Memo1's activity
in cancer development.

Pernilla Wittung-Stafshede said: "When we expand the basics of the action of copper-binding proteins in cancer cells, we also open the door
to new treatments.
"

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