Nature Cell Biology 2, pp 76 - 83

Tumour cells often lose their ability to adhere to neighbouring cells and to extracellular structures, which has two immediate consequences: first, such cells cannot regulate the rate of their proliferation in response to environmental signals anymore and they continue to proliferate in an overcrowded environment; second, these cells migrate, with the tumour colonizing other organs, a process known as metastasis.

This is because mutations arising either in genes corresponding to proteins which are responsible for cell adhesion, such as the E-cadherin protein, or in genes corresponding to proteins which regulate the expression these proteins.

In Nature Cell Biology [February 2000], Angela Nieto and her colleagues at Instituto Cajal, Madrid and Antonio Garcia de Herreros and his colleagues at Universitat Pompeu Fabra, Barcelona, Spain now show that tumours with reduced expression of E-cadherin often also show increased expression of another protein, Snail. They further show that Snail directly prevents expression of the E-cadherin gene, and 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, which paves the way for the design of anti-metastatic drugs.

What is also interesting is that this pathological process also occurs during normal embryonic development: neural cells transiently shut express the Snail protein and conversely shut down the expression of E-cadherin when they migrate from their location of origin to their ultimate location. Thus spacio-temporal control of the expression of the E-cadherin protein is a key switch from adhesion to migration that has been taken advantage of by tumour cells.

Nature Cell Biology 2, pp 70 - 75

In the early days of molecular biology, genes were first defined by the description of a mutant; and cloning the gene from there was a long and tedious process. But at least the phenotype of the mutant (i.e. what seemed to be different in the mutant as compared to a normal individual) was a clue to the function of the gene. Things changed with technology, and with the combination of large scale genome sequencing programs and computarized processing of the sequence, but the limiting step was then to identify the function of such genes. The best way so far to assess the function of a gene is to get rid of it, and see what happens. But this is more easily said than done, particularly in Mammals.

Florence Wianny and Magdalena Zernicka-Goetz at the Wellcome/CRC Institute of Cambridge University now report in Nature Cell Biology [February 2000] that, contrary to what was thought and feared, this could be achieved as ‘easily’ in mice as in lower species. Indeed, RNAi, a technique initially described in the worm C.elegans has now been shown to be applicable to mouse embryos as well. RNAi consists in neutralizing the intermediate product between the gene (the information) and the protein (the functional unit) the RNA, thus preventing expression of the protein corresponding to that gene.

This is excellent news for scientists working with mammalian cells!

RNAi in mice promises to be very widely used and to substantially speed up the process of post-genomics, the analysis of the information generated by the genome sequencing projects.