Proteins that bind copper ions are necessary for the growth and dissemination of cancer cells throughout the body. Possible new therapeutic targets have been discovered as a result of recent research on the interactions between proteins and how they bind to metals in cancer-related proteins.
Human cells need trace amounts of the element copper to carry out necessary biological processes. Studies showing increased copper levels in tumor cells and blood serum from cancer patients have led researchers to the conclusion that cancer cells require more copper than healthy cells do. Additionally, when copper levels are higher, more copper-binding proteins are active.
"Therefore, these proteins are highly important to study when it comes to understanding the development of cancer and deeper knowledge about them can lead to new targets for the treatment of the disease," said Pernilla Wittung-Stafshede, Professor of Chemical Biology at Chalmers University of Technology, Sweden.
Most cancer-related deaths are due to the fact that metastases - secondary tumours - form in several places in the body, for example, in the liver or lungs. A protein called Memo1 is part of the signalling 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 Chalmers research team was interested in learning more about the relationship between copper and Memo1. In a recent study, the researchers used a series of test tube experiments to investigate the Memo1 protein's capacity to bind copper ions. They learned that the protein exclusively binds copper in its reduced state. The most prevalent type of copper ions in living cells is this one. It's a significant discovery since, despite being required by the body, reduced copper also contributes to redox events that harm or even kill cells. The scientists discovered that Memo1 prevented copper's harmful redox reactions when it interacted with the metal.
"This poses a risk for the tumour 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.
The researchers also saw that Memo1 can form a complex with another copper-binding protein found in our cells - Atox1. It is a copper transporter inside human cells and the research team has previously shown that Atox1, with the help of copper, contributes to breast cancer cells being able to move and form metastases. Overall, the findings in the new study mean that copper and copper-binding proteins could be targets for future cancer treatment.
"We saw how copper ions 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.
The researchers now want to move forward with determining the copper ion binding sites in Memo1, and how the presence of copper affects Memo1's activities in cancer development.
"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.
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