2014/06/20

A possible pathway for inhibiting liver and colon cancer growth is found

- A study by CIC bioGUNE, the University of Liverpool and the US research centre USC-UCLA has revealed the structure of a protein complex involved in these diseases

- This discovery will help to determine which part of the protein will need to be blocked to halt the growth of cancer cells

- This study has recently been published in the International Union of Crystallography's journal IUCrJ

(Bilbao, June 2014).- An international team of experts from Bilbao, California and Liverpool has unravelled the mechanism by which two proteins, namely MAT alpha 2 and MAT beta, bind to each other, thereby promoting the reproduction of tumour cells in liver and colon cancers. This discovery opens up future research into drugs that act on the binding of these proteins, thereby possibly inhibiting cancer cell growth.

The role played by these proteins in the cell is determined by how these proteins come together and work in concert. As a result of this discovery, it is now known which part of their respective structures can be blocked to prevent these proteins from joining together. This is very important as, when these proteins bind to each other, the production of a molecule known as SAMe, which plays a role in uncontrolled tumour cell growth, increases considerably. Although the relationship between SAMe and tumour growth has been known for some time, this molecule also has other important functions inside the cell that cannot be altered, and there is currently no way of acting against it without affecting these other life-sustaining functions.

However, MAT alpha 2 and MAT beta are only overexpressed in adults with tumours, thereby representing an excellent therapeutic target which could open the door to the creation of drugs that act exclusively by blocking those regions that allow their mutual binding. This hypothetical treatment would inhibit tumour growth-it should be remembered that tumours are a mass of cells that grow without control-and would have the additional advantage that it would not cause any damage to the body.

The international partnership between three teams has thus opened the way to fighting against liver and colon cancers, where the presence of this protein complex is highest. Both these tumours are of great social and clinical relevance. Indeed, in 2012 liver cancer was responsible for the second highest number of deaths worldwide, with colon cancer appearing in third place.

This research involved the use of X-ray crystallography and solution X-ray scateering techniques utilizing some of Europes's most powerful X-ray synchrotron sources, ALBA in Spain, SOLEIL in France and DIAMOND in the UK. The study was recently published in the July issue of the new journal, IUCrJ, launched by the International Union of Crystallography (IUCr) as part of the International Year of Crystallography.

The CIC bioGUNE researcher Adriana Rojas, who led this study, acknowledges that "this work would not have been possible without the more than 30 years of research dedicated by José María Mato to the field of liver cancer and, specifically, the molecule SAMe".

"Many years have passed since it was first understood which proteins produce SAMe and how the levels of this molecule affect cancer cell growth, and we have now shown that the complex between MAT alpha 2 and MAT beta is a possible therapeutic target", notes Dr. Rojas.

- About CIC bioGUNE

The Center for Cooperative Research in Biosciences (CIC bioGUNE) is a biomedical research organization established by the Basque Government's Department of Industry in 2002. The main goal of this body, which is located at the Bizkaia Technology Park, is to make progress in basic research in the field of bioscience.