Key Molecules In Cancer Spread Uncovered

Main Category: Cancer / Oncology
Article Date: 10 Sep 2009 - 9:00 PDT

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Scientists at The Institute of Cancer Research (ICR) have shed new light on a group of molecules crucial to cancer spread, according to research published today in the journal Science.

The study brings hope that a drug will be developed to fight the spread of cancer, known as metastasis, which is responsible for 90 per cent of all cancer patient deaths.

The interaction between the Rho family of proteins and the DOCK family of proteins is critical for the cancer cells to change shape and spread through the body. DOCK proteins are known to activate, or switch on, Rho proteins, but until now scientists have not understood exactly what was happening between these molecules.

In a study funded by Cancer Research UK, ICR Professor of Molecular Biology David Barford and his team mapped the interaction between one DOCK protein and a corresponding Rho protein in three dimensions. They created detailed images of how the molecules slot together at each step of the process.

"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," Professor Barford says.

" 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."

Professor Chris Marshall, study co-author and Director of the Cancer Research UK Centre for Cell and Molecular Biology at the ICR, added: "Understanding and tackling metastasis is one of the most important areas of our 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."

Note

- High resolution images of the protein interactions are available on request
- The family of proteins known as Rho GTPase (Rho guanosine triphosphatases) help cancer cells change shape, allowing them to spread through the body. The DOCK family of proteins also play a role in this process as they are responsible for turning on and off the Rho proteins, but until now scientists have not known exactly how this occurs. The ICR team used structural analysis to find a nucleotide sensor on DOCK9 that contributes to the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP), setting off a biological chain reaction that ends with Rho GTPase Cdc42 being switched on.

Source
The Institute of Cancer Research
Cancer Research UK

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