Tumour cells often lose their ability to stick to neighbouring cells and other structures outside the cell. This has two immediate consequences. First, tumour cells cannot regulate the rate of their proliferation in response to environmental signals, as normal cells can, and so they continue to amass in an overcrowded environment. Second, these cells migrate and the tumour colonizes other organs -- a process known as 'metastasis'. Now Angela Nieto and her colleagues at Instituto Cajal, Madrid, Spain, and Antonio Garcia de Herreros and his colleagues at Universitat Pompeu Fabra, Barcelona, Spain, give new insight into how this happens.

Tumour formation is a sequential process due to the accumulation of mutations that affect key cellular functions. Because most mutations arise during cell division when the DNA is copied -- a process with inherent chances of errors being introduced -rapidly dividing cells accumulate yet more mutations. The most obvious mutations impair the capacity of the cell to adhere to its environment, leading cancer to spread to other organs. The manufacture of proteins responsible for adhesion of cells to other cells and to other structures is reduced in metastasising cells (migrating tumour cells). This is due to the emergence of mutations either in a gene corresponding to a protein known as 'E-cadherin', or in genes that affect proteins that regulate the expression of E-cadherin.

In Nature Cell Biology1, Nieto and Herreros' groups show that tumours with reduced expression of E-cadherin also often show increased expression of another protein, 'Snail'. As Snail is known to be a regulator of the expression of certain genes, the researchers thought that this protein might be responsible for the decreased expression of E-cadherin, and they show that this is indeed the case: Snail directly prevents expression of the E-cadherin gene.

They go on to demonstrate that they can prevent the decreased expression of E-cadherin -- and the consequences thereof in terms of adhesion and cell migration -- by interfering with the expression of Snail. This could pave the way for the design of new anti-cancer drugs.

Interestingly, something like this also occurs during normal embryonic development. When neural cells migrate from their origin to their ultimate location, they transiently change shape, and their adhesion and migration properties change (a process technically known as 'epithelium-mesenchymal-transition'). This is because they shut down the expression of E-cadherin at the onset of migration, apparently via a sharp, transient increase in the expression of the E-cadherin-repressor, Snail. Thus, control of the expression of the E-cadherin protein in time and space is a key switch between adhesion and migration that is hijacked by tumour cells.