A paracrine requirement for hedgehog signalling in cancer

Robert L. Yauch, 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 and Frederic J. de Sauvage ()
Additional contact information
Robert L. Yauch: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Stephen E. Gould: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Suzie J. Scales: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Tracy Tang: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Hua Tian: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Christina P. Ahn: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Derek Marshall: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Ling Fu: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Thomas Januario: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Dara Kallop: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Michelle Nannini-Pepe: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Karen Kotkow: Curis Inc., 45 Moulton Street, Cambridge, Massachusetts 02138, USA
James C. Marsters: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Lee L. Rubin: Curis Inc., 45 Moulton Street, Cambridge, Massachusetts 02138, USA
Frederic J. de Sauvage: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA

Nature, 2008, vol. 455, issue 7211, 406-410

Abstract: Hedgehog signalling in cancer The hedgehog (Hh) signalling pathway acts in the developing embryo as part of the network controlling cell proliferation and cell fate. It has also been implicated in a number of solid tumours, where it was thought to mediate tumour cell proliferation directly. But a new study suggests a rather different role for hedgehog in cancers. Hedgehog ligands secreted by cancer cells failed to activate signalling in tumour epithelial cells but instead acted on the stroma, the mass of extracellular matrix, fibroblasts, endothelial cells and microvasculature in which the malignant cells are embedded. Tumour growth was promoted, but apparently via an effect on the tumour cells' microenvironment. These findings have important implications for the use of hedgehog antagonists as anticancer drugs.

Date: 2008
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DOI: 10.1038/nature07275

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