UK scientists uncover crucial mechanism for cancer spread

In collaboration with the Press Association

A study funded by Cancer Research UK has shed light on a group of proteins that are involved in the spread of cancer - a process known as metastasis.

Previous research has shown that the interaction between the Rho GTPase and DOCK families of proteins is critical for cancer cells to change shape and spread from the initial tumour site.

The Rho proteins help cancer cells to change shape so that they can spread through the body, while the DOCK proteins switch the Rho proteins on.

Previously, scientists did not understand how the DOCK proteins did this, but the latest study, which is published in the journal Science, has revealed how it happens.

Using an electron microscope, scientists at The Institute of Cancer Research (ICR) have created detailed 3D images of the way in which a single DOCK protein interacts with a corresponding Rho protein.

They identified a nucleotide sensor on the DOCK protein that helps to replace a guanosine diphosphate (GDP) molecule for a guanosine triphosphate (GTP) molecule - an event that ultimately leads to the Rho protein being switched on.

The advance increases understanding of the fundamental process that governs cancer spread, and takes researchers a step closer to developing drugs that block this process, which is responsible for the vast majority of all deaths from the disease.

Professor David Barford, professor of molecular biology at the ICR, explained: "We've known for some time that DOCK proteins help control the movement of cancer cells when they try to spread throughout the body and invade other organs, making them a very attractive target for the development of new drugs to prevent metastasis.

"Yet despite their important biological role, little was understood about how exactly DOCK proteins operated. By unravelling this mechanism, we have paved the way for the development of a drug that could effectively stop metastasis."

Study co-author Professor Chris Marshall, director of the Cancer Research UK Centre for Cell and Molecular Biology at the ICR, noted that tackling metastasis is one of the most important areas of the team's research.

"DOCK proteins are key components of metastasis and our new knowledge of how they operate will help us achieve our vision for people to live their lives free from the fear of cancer as a life-threatening disease," he added.