A paracrine requirement for hedgehog signalling in cancer - PubMed (original) (raw)

. 2008 Sep 18;455(7211):406-10.

doi: 10.1038/nature07275. Epub 2008 Aug 27.

Stephen E Gould, Suzie J Scales, Tracy Tang, Hua Tian, Christina P Ahn, Derek Marshall, Ling Fu, Thomas Januario, Dara Kallop, Michelle Nannini-Pepe, Karen Kotkow, James C Marsters, Lee L Rubin, Frederic J de Sauvage

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A paracrine requirement for hedgehog signalling in cancer

Robert L Yauch et al. Nature. 2008.

Abstract

Ligand-dependent activation of the hedgehog (Hh) signalling pathway has been associated with tumorigenesis in a number of human tissues. Here we show that, although previous reports have described a cell-autonomous role for Hh signalling in these tumours, Hh ligands fail to activate signalling in tumour epithelial cells. In contrast, our data support ligand-dependent activation of the Hh pathway in the stromal microenvironment. Specific inhibition of Hh signalling using small molecule inhibitors, a neutralizing anti-Hh antibody or genetic deletion of smoothened (Smo) in the mouse stroma results in growth inhibition in xenograft tumour models. Taken together, these studies demonstrate a paracrine requirement for Hh ligand signalling in the tumorigenesis of Hh-expressing cancers and have important implications for the development of Hh pathway antagonists in cancer.

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