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Hedgehog signalling in prostate regeneration, neoplasia and metastasis

Author

Listed:
  • Sunil S. Karhadkar

    (The Johns Hopkins University School of Medicine
    The Johns Hopkins University School of Medicine)

  • G. Steven Bova

    (The Johns Hopkins University School of Medicine
    The Johns Hopkins University School of Medicine
    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
    The Johns Hopkins University School of Medicine)

  • David M. Berman

    (The Johns Hopkins University School of Medicine
    The Johns Hopkins University School of Medicine
    The Johns Hopkins University School of Medicine
    The Johns Hopkins University School of Medicine)

  • Philip A. Beachy

    (The Johns Hopkins University School of Medicine
    The Johns Hopkins University School of Medicine)

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.

Suggested Citation

  • Sunil S. Karhadkar & G. Steven Bova & Nadia Abdallah & Surajit Dhara & Dale Gardner & Anirban Maitra & John T. Isaacs & David M. Berman & Philip A. Beachy, 2004. "Hedgehog signalling in prostate regeneration, neoplasia and metastasis," Nature, Nature, vol. 431(7009), pages 707-712, October.
    • Handle: RePEc:nat:nature:v:431:y:2004:i:7009:d:10.1038_nature02962
    DOI: 10.1038/nature02962
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    Cited by:

    1. Mark W. Youngblood & Zeynep Erson-Omay & Chang Li & Hinda Najem & Süleyman Coșkun & Evgeniya Tyrtova & Julio D. Montejo & Danielle F. Miyagishima & Tanyeri Barak & Sayoko Nishimura & Akdes Serin Harma, 2023. "Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Hai-Bo Zhang & Xiao-Bao Ding & Jie Jin & Wen-Ping Guo & Qiao-Lei Yang & Peng-Cheng Chen & Heng Yao & Li Ruan & Yu-Tian Tao & Xin Chen, 2022. "Predicted mouse interactome and network-based interpretation of differentially expressed genes," PLOS ONE, Public Library of Science, vol. 17(4), pages 1-16, April.

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