Skin formation mechanisms revealed, promise progress in cancer fight

Scientists in Italy have discovered two proteins that control the formation of skin cells from stem cells deposited at the base of the skin. The discovery raises hopes for the fight against a variety of epithelial cancers. Now published in Nature Cell Biology, the study received partial financial support from different projects funded under the EU's Sixth Framework Programme (FP6).

Together with colleagues from the Spain-based CIEMAT (Centro de Investigaciones Energéticas, Medioambientales y Tecnologicas), Dr Claus Nerlov of the European Molecular Biology Laboratory (EMBL) and his group in Monterotondo, Italy, studied a family of proteins dubbed C/EBP (CCAAT-enhancer-binding proteins), already known to regulate similar mechanisms in other types of stem cells. As they deleted the corresponding genes in mouse embryos, they found that in fact two proteins out of this family triggered the differentiation from multipotent stem cell to skin cell, C/EBP alpha and beta.

"Mice with neither C/EBP alpha nor beta had taut and shiny skin that couldn't keep the water inside their bodies," Dr Claus Nerlov explains. "They lacked many of the proteins that make skin mechanically strong and water tight, and they died of dehydration shortly after birth."

Yet the presence of only one of the proteins was sufficient to prevent this malformation. This unexpected redundancy might be due to different mechanisms, the researchers theorise. For instance, it might add an extra layer of control on cell proliferation, in order to help avoid problems such as cancer. On the other hand, it might indicate that the two proteins have different functions in other situations.

Most importantly, however, the improved understanding of these proteins and their determining role in when and how epithelial stem cells turn into skin cells spells progress for the treatment of epithelial cancers, including not only skin, but also breast and oral cancers. The shared characteristic in these cancer types is that they have genes turned on that would normally only be expressed in embryonic stem cells. This feature is likely to help malignant cells multiply indefinitely.

"This is a very important discovery," Dr Nerlov emphasises. "It opens up a lot of new areas, because we can see how these proteins control virtually every other molecule known to regulate skin cell differentiation. It seems to be a key piece in the puzzle of how our skin is formed and maintained throughout life."

In addition to national funding, this research was supported by the European Commission through the EUROSTEMCELL ('European consortium for stem cell research') and EUROCSC (Targeting cancer stem cells for therapy) projects, as well as the Marie Curie mobility scheme.

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