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ARS Home » Pacific West Area » Logan, Utah » Poisonous Plant Research » Research » Publications at this Location » Publication #170208
Title: HEDGEHOG SIGNALLING IN PROSTATE REGENERATION, NEOPLASIA AND METASTASIS

Author
item KARHADKAR, SUNIL - HOWARD HUGHES MED INS CEN
item BOVA, G. - HOWARD HUGHES MED INSTI
item ABDALLAH, NADIA - HOWARD HUGHES MED INST
item DHARA, SURAJIT - HOWARD HUGHES MED INST
item Gardner, Dale
item MALTRA, ANIRBAN - HOWARD HUGHES MED INSTIT
item ISAACS, JOHN - JOHN HOPKINS UNIV SCH MED
item BERMAN, DAVID - JOHN HOPKINS UNIV SCH MED
item BEACHY, PHILLIP - JOHN HOPKINS UNIV SCH MED

Submitted to: Nature
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/23/2004
Publication Date: 9/12/2004
Citation: Karhadkar, S.S., Bova, G.S., Abdallah, N., Dhara, S., Gardner, D.R., Maltra, A., Isaacs, J.T., Berman, D.M., Beachy, P.A. 2004. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature.

Interpretive Summary: Metastatic cancers adopt certain properties of normal cells in developing or regenerating organs. We report here that activity of the Hedgehog (Hh) signalling pathway is required for regeneration of prostate progenitor cells and renders them tumorigenic. Elevated pathway activity furthermore distinguishes metastatic from localized prostate cancer, and pathway manipulation using cyclopamine can modulate invasiveness and metastasis. Monitoring and manipulating the Hh pathway activity may thus offer significant improvements in diagnosis and treatment of prostate cancers with metastatic potential.

Technical 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 patterning, is required for regeneration of 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, and essential Hh response component that is not expressed in benign prostate epithelial cells. Monitoring and manipulating the Hh pathway activity may thus offer significant improvements in diagnosis and treatment of prostate cancers with metastatic potential.