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Hedgehog Wnteraction in colorectal cancer
  1. G R van den Brink1,
  2. J C H Hardwick2
  1. 1Department of Experimental Internal Medicine, Academic Medical Centre, Amsterdam, the Netherlands, and Department of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland
  2. 2Department of Experimental Internal Medicine, and Department of Gastroenterology, Academic Medical Centre, Amsterdam, the Netherlands
  1. Correspondence to:
    Dr G R van den Brink
    Laboratory for Experimental Internal Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; g.r.vandenbrink{at}

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The Hedgehog pathway was recently shown to antagonise constitutive activity of the Wnt pathway that drives proliferation of colorectal cancer cells. Studies in this issue of Gut refine our understanding of the underlying mechanism and provide evidence for such antagonism in colorectal cancers in vivo

The mucosa of the colon is covered by a single layer of epithelial cells that is replaced once every 3–7 days. New cells are produced by a pool of progenitor cells that lie at the base of small mucosal invaginations called crypts. It has been estimated that these progenitor cells generate approximately 10 billion new cells per day in the human colon.1 Homeostasis in such a massive process of regeneration can only be achieved if the behaviour of cells in the system is not regulated at the level of the individual cell (intrinsic). Instead, the fate of individual epithelial cells must be determined by extra cellular (extrinsic) signals that are generated at the population level. It is now becoming clear that these extrinsic signals are provided by morphogens, a class of molecules that has been identified by developmental biologists who studied patterning events during embryogenesis.2 Morphogens are soluble proteins that form long range concentration gradients and act in a dose dependent manner to induce distinct cellular responses on their target cells. In this way, cellular fate is determined by the distance of a target cell from the source of the morphogen. Several morphogens have now been identified as regulators of cell fate in the adult colon.

The Wnt pathway (fig 1) was the first morphogenetic pathway that was implicated in colonic epithelial homeostasis when it was found that adenomatous polyposis coli (APC) acts as an important regulator of Wnt signalling.3APC had initially been identified as the gene mutated in patients with …

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  • Conflict of interest: None declared.

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