Researchers find why Cancer cells require proteins, copper

Small amounts of the metal copper are required by human cells to perform essential biological functions. The conclusion drawn from studies demonstrating higher copper levels in tumor cells and blood serum from cancer patients is that cancer cells require more copper than healthy cells. Additionally, more copper-binding proteins are active when copper levels are higher.

Most cancer-related deaths are due to the fact that metastases – secondary tumors – form in several places in the body, for example, in the liver or lungs. A protein called Memo1 is part of the signaling systems that cancer cells use to grow and spread around the body. Previous research has shown that when the gene for Memo1 is inactivated in breast cancer cells, their ability to form metastases decreases.

A research group from Chalmers wanted to take a closer look at the connection between Memo1 and copper. In a new study published in the scientific journal PNAS, the researchers examined the Memo1 protein’s ability to bind copperions through a series of test tube experiments. They discovered that the protein binds copper, but only the reduced form of copper. It is this form of copperions that is most common in living cells. It’s an important discovery because reduced copper, while it is needed in the body, also contributes to redox-reactions that damage – or even kill – the cells. The researchers found that when Memo1 interacted with copper, the metal’s toxic redox reactions were blocked.

“This poses a risk for the tumor to be dependent on a lot of copper because it can provoke chemical reactions that are harmful to the cancer cells. We believe that Memo1, by binding copper when needed, protects the cancer cells so that they can continue to live and spread,” said Pernilla Wittung-Stafshede, who is one of the study’s lead authors.

“We saw how copperions could transfer between the proteins Memo1 and Atox1 in test tubes, and when we looked in breast cancer cells, we found that the two proteins were close to each other in space. Based on this, we conclude that the exchange of copper between these proteins can take place in cancer cells as well as in test tubes and thus be of biological relevance,” says Pernilla Wittung-Stafshede.

“When we expand our basic knowledge of the role of copper-binding proteins in cancer cells, we also open the door to new treatments,” said Pernilla Wittung-Stafshede.