Hedgehog signalling in prostate regeneration, neoplasia and metastasis

Sunil S. Karhadkar, G. Steven Bova, Nadia Abdallah, Surajit Dhara, Dale Gardner, Anirban Maitra, John T. Isaacs, David M. Berman () and Philip A. Beachy ()
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Sunil S. Karhadkar: The Johns Hopkins University School of Medicine
G. Steven Bova: The Johns Hopkins University School of Medicine
Nadia Abdallah: The Johns Hopkins University School of Medicine
Surajit Dhara: The Johns Hopkins University School of Medicine
Dale Gardner: Poisonous Plant Research Laboratory
Anirban Maitra: The Johns Hopkins University School of Medicine
John T. Isaacs: The Johns Hopkins University School of Medicine
David M. Berman: The Johns Hopkins University School of Medicine
Philip A. Beachy: The Johns Hopkins University School of Medicine

Nature, 2004, vol. 431, issue 7009, 707-712

Abstract: Abstract Metastatic cancers adopt certain properties of normal cells in developing or regenerating organs, such as the ability to proliferate and alter tissue organization. We find here that activity of the Hedgehog (Hh) signalling pathway, which has essential roles in developmental patterning1,2,3,4,5,6, is required for regeneration of prostate epithelium, and that continuous pathway activation transforms prostate progenitor cells and renders them tumorigenic. Elevated pathway activity furthermore distinguishes metastatic from localized prostate cancer, and pathway manipulation can modulate invasiveness and metastasis. Pathway activity is triggered in response to endogenous expression of Hh ligands, and is dependent upon the expression of Smoothened, an essential Hh response component1,2,7 that is not expressed in benign prostate epithelial cells. Monitoring and manipulating Hh pathway activity may thus offer significant improvements in diagnosis and treatment of prostate cancers with metastatic potential.

Date: 2004
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DOI: 10.1038/nature02962

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