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Activation of Hedgehog Signaling in Human Cancer

  • Jingwu XieEmail author
  • Ervin Epstein
Chapter

Abstract

Hedgehog gene was first described in Drosophila in 1980 by Nobel laureates Drs. E. Wieschaus and C. Nusslein-Volhard. Over the past three decades, the hedgehog pathway has been shown to be a major regulator for cell differentiation, tissue polarity, cell proliferation, stem cell maintenance, and carcinogenesis. The first link of Hh signaling to human cancer was established in 1996 through studies of a rare familiar disease, Gorlin syndrome. Follow-up studies from many laboratories reveal activation of this pathway in a range of human cancer types, including basal cell carcinomas (BCCs), medulloblastomas, leukemia, gastrointestinal, lung, ovarian, breast, and prostate cancers. Targeted inhibition of Hh signaling is now believed to be effective in treatment and prevention of human cancer. Even more exciting is the discovery and synthesis of a variety of specific inhibitors for this pathway. In this review, we summarize major advances in our understanding of Hh signaling activation in human cancer, useful mouse models for studying Hh-mediated carcinogenesis, the roles of Hh signaling in tumor initiation, promotion, tumor metastasis, and cancer stem cell maintenance as well as antagonists for Hh signaling and their clinical implications.

Keywords

Hedgehog Smoothened PTCH1 Cancer Basal cell carcinomas Signal transduction Clinical trials and animal model 

Notes

Acknowledgments

Current research in my laboratory is supported by grants from the National Cancer Institute CA94160 and Wells Center for Pediatric Research.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisUSA

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