Scientists at the University of Dundee have gained new insight into the working of an important tumor suppressor, called PTEN, which is involved in at least a quarter of all cancers. Their study, published in Science Signaling, discovered that when ‘turned off’ or damaged PTEN drives the development of many cancers.
The team, led by Dr. Nick Leslie, discovered that even though some damaged PTEN proteins still remain functioning mostly normal, they lose the ability to stop cancer cells invading the brain.
Brain tumors are particularly fatal. Given that they rarely spread outside the brain, by the time they are diagnosed, cancers cells have generally moved away from the original tumor and spread into the surrounding brain tissue, leading to a very poor prognosis. If the original tumor is surgically removed, it often does not take long before a second tumor grows from the few cancer cells in the surrounding brain tissue.
Dr. Leslie’s team experimented with a 3D matrix similar to that found between cells in the brain, to explore the cancer cells process of invading healthy tissue from a tumor. They observed how PTEN controls the growth process of these brain tumors, how they change their shape, switching specific genes on and off and significantly, how PTEN generally inhibits this invasion process.
Dr. Leslie commented:
“We know that PTEN has lots of effects on what cells do, but it has proved harder to be certain which of these effects are important in stopping cancer and therefore which ones we should develop drugs to target. It is really important we understand the factors driving these cancers, which affect thousands of people every year in the UK.”
He stated that although a lot of knowledge already exists about one of the ways in which PTEN can prevent the growth and division of cells, there have been several clues in the past that there are other unknown ways in which PTEN may stop cancers developing, saying:
“In our new work, we’ve used two similarly damaged versions of PTEN, one of which was found in a tumor, that we show can still do the best recognized things that PTEN does, just as well as normal PTEN protein. However, these damaged proteins have completely lost the ability to stop brain tumors cells invading through a 3D matrix. This implies that in some, and perhaps many, tumors it is not the best known things that PTEN does that explain why it gets damaged, but instead it must be these new ways that PTEN can work that we know much less about.”
They also discovered a ‘gene signature’ controlled by PTEN, i.e. displaying which genes are turned on and off in particular cells, which is linked to PTENs function of invasion control. However, they did not observe precisely how it worked.
Dr. Leslie concluded:
“Interestingly this gene signature also seemed to be recognizable in almost all of a large set of human brain tumor samples that lack or have damaged PTEN, providing more evidence that this new way in which PTEN works may be important in brain tumor development. The key goals of future work in this area need to include understanding much more about these new ways in which PTEN can work and whether they show us new ways to develop drugs to treat brain and other tumors.”
Written by Petra Rattue