Inappropriate activation of a signalling pathway in intestinal stem cells causes them to become cancerous. The findings, reported in two Nature papers this week, help identify the cell type at the root of this cancer, which should in turn aid therapeutic design.
Genetic mutations that activate the Wnt signalling pathway are known to trigger intestinal cancer; however, it's not clear which cells are responsible. Hans Clevers and colleagues switched on the Wnt pathway in cells expressing the receptor Lgr5 - a marker for intestinal stem cells - and found that this was sufficient to initiate tumour formation.
In a related paper, Richard Gilbertson and colleagues report that Lgr5-expressing intestinal stem cells also express the cell surface glycoprotein prominin 1. These prominin-1-expressing stem cells also form intestinal tumours when the Wnt pathway is abnormally activated. The research highlights Lgr5 and prominin 1 as potential markers for identifying cancer-prone stem cells.
Hans Clevers (Hubrecht Institute, Utrecht, Netherlands) Author paper 
Richard Gilbertson (St Jude Children's Research hospital, Memphis, TN, USA) Author paper 
Abstracts available online:
(C) Nature press release.
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