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The 'cancer magnet' protein

Friday 13 March 2009

Scientists have discovered “a protein magnet”, believed to be key to stopping cancer spreading around the body, The Daily Telegraph has reported. The newspaper says this research could lead to new drugs that stop cancer cells spreading around the body to form new tumours at different sites.

This research looked at cancer cells in the laboratory to uncover a critical step in the process that breaks the links between the cells. It found a complex set of interactions that enables one particular protein, called Tiam1, to attract other proteins “like metal to a magnet”.

The research also shows that Tiam1, which is crucial for preserving the links between cells, can be destroyed, thus breaking the bonds between cancer cells. Theoretically, these unattached cancer cells  could then spread around the body to cause secondary tumours. The researchers speculate that in the future, drugs could stop the destruction of Tiam1 and potentially stop cancer spreading. 

This is an important first step in understanding how the spread of cancer might be prevented. No specific drugs are suggested to prevent Tiam1 destruction, so research to identify suitable drugs will surely be on its way.

Where did the story come from? 

This research was carried out by Dr Simon A. Woodcock and research colleagues from Cancer Research UK, Paterson Institute for Cancer Research at the University of Manchester, and the University of Athens. The study was supported by Cancer Research UK and the European Commission, and published in the peer-reviewed journal Molecular Cell.

What kind of scientific study was this?  

This research involved a complex set of laboratory studies to investigate the interactions of several proteins that are involved in cancerous cells spreading around the body.

Some proteins have a role in joining individual cells together within tissue. The Tiam1 protein was originally identified in T-lymphoma cells and has now been shown in other cells to have a direct role in establishing and maintaining one type of connection between neighbouring cells, called the adherens junction (AJ). Along with other proteins, Tiam1 plays an essential role in preserving the links between cells at this junction.

Another protein, known as the oncoprotein (Src) is known to have the opposite effect to Tiam1, and causes these AJ junctions to disassemble, breaking cells apart and allowing them to migrate. This process occurs during normal development of the body and in the healing of wounds, but can also occur when cancerous cells spread around the body.

The Src protein functions by attaching a type of chemical called a phosphate group to other proteins in the cell, a process called “phosphorylation”. This addition of a phosphate group causes these proteins to function differently. The researchers thought that the Src protein might cause the AJ to break down by adding a phosphate group to the Tiam1 protein.

The researchers performed several experiments in test tubes and in cells grown in the laboratory to test their theory. They also further investigated which other proteins are involved in this process, and how phosphorylation affects their interaction.

Finally, they looked at tissue taken from various human cancers (lung cancer, bowel cancer, and head and neck cancers) to see whether the Tiam1 in these tissues was phosphorylated, and whether active Src protein could also be found in these tissues.

What were the results of the study?

The researchers found that in both test tubes and lab-grown cells, the Src protein did attach a phosphate group to the Tiam1 protein at the adherens junction. This reaction triggered the breakdown of the junction, and allowed cells to migrate away from each other. They also found that addition of a phosphate group to the Tiam1 protein would cause it to break down in the cell.

The researchers also investigated the other proteins involved in this chain reaction that are programmed to destroy Tiam1. When they looked at tissue samples from three types of human cancer, they found that the active Src protein and the phosphorylated Tiam1 protein were both present in cancerous tissue but not in neighbouring normal tissue. The amount of phosphorylated Tiam1 protein in the cells was strongly related to the amount of active Src protein present.

What interpretations did the researchers draw from these results?  

The researchers say that they have found proteins involved in a chain reaction programmed to destroy Tiam1, and therefore they have found an important mechanism that contributes to the spread of cancer. This destruction of the Tiam1 protein in turn breaks the bonds between cancer cells, allowing them to spread around the body.

These findings, the researchers say, could help scientists develop drugs that stop the destruction of Tiam1 and potentially stop the spread of cancer.

The authors conclude that their analysis of the mechanisms of Tiam1 and Src in various types of cancer tissue demonstrates  a “potential to operate during the progression of cancers in man”. This means that they are hopeful that the improved understanding of the mechanisms involved may also be relevant to understanding how cancers progress in humans.

What does the NHS Knowledge Service make of this study?  

This is extensive and complex cellular research in which the researchers have provided an original article aimed at the scientific reader. Cancer Research UK has also produced a press release, which explains the significance of this research in simple terms and explains its future potential.

The researchers hope that if they could harness the effects seen in the protein interactions they could “restore the links between cells and potentially stop cancer spreading".

Because cancer is more likely to be successfully treated when the disease is caught early and has not spread, cancer research is focusing strongly on understanding how and why cancer cells break away from the primary tumour and spread, causing secondary tumours in other parts of the body.

The director of cancer information at Cancer Research UK says, "While we're yet to see if this research can be translated into drugs to stop the process, this adds to our understanding of this crucial area of cancer research."

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Protein 'magnet' to stop cancer spreading around body discovered.

The Daily Telegraph, 13 March 2009

Links to the science

Woodcock SA, Rooney C, Liontos M et al.

Src-Induced Disassembly of Adherens Junctions Requires Localized Phosphorylation and Degradation of the Rac Activator Tiam1.

MolCel Volume 33, Issue 5, 13 March 2009, Pages 639-653