Cancer Research UK scientists have unlocked the secrets of proteins involved in tumour cells creeping away from the original tumour and spreading around the body. Their findings are published in Molecular Cell today.
The study involves a protein called Tes which appears to block cell growth and prevent tumours from forming. Scientists have now shown that it locks onto Mena – a protein involved in cell crawling that is found in excessive amounts in tumours.
This is exciting because Tes binds to Mena in an unexpected way compared with other proteins that interact with Mena.
Crucially, when Tes binds to Mena, it stops cells from crawling as it blocks Mena from sticking to its usual binding partners.
The discovery offers the possibility of the development of drugs which could block the action of Mena by mimicking the action of Tes.
The movement of cells from the primary tumour to other parts of the body is the main reason that cancer can be so difficult to treat. Preventing this is one of the major challenges for researchers.
Dr Michael Way, lead author based at Cancer Research UK’s London Research Institute, said: “Our findings represent a new way to regulate of a key family of proteins involved in cell crawling that will change the way researchers see current models of cell migration – an important aspect of the spread of cancer.”
Dr Lesley Walker, director of science information at Cancer Research UK, said: “Cancer cells use many complex processes when they break away from their tumour and spread to other areas of the body. Understanding these mechanisms and increasing our knowledge about this protein can hopefully help us to develop more effective cancer treatments in the future.”
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Tes binds to Mena at a particular point called the EVH1 domain. Proteins normally lock onto Mena through a sequence called FPPPP, which binds to the EVH1 domain. Researchers in this paper show that Tes, which doesn’t have the FPPPP sequence, can still bind to Mena via the EVH1 domain, blocking its action.
The researchers in this study looked at specific binding regions of the proteins using a number of techniques, including x-ray crystallography. This helped them determine the precise details of how the proteins interact and the effects on other proteins crucially involved in cell migration and cancer spread.
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