The Hedgehog pathway: role in cell differentiation, polarity and proliferation

Yanfei Jia, Yunshan Wang, Jingwu Xie

Research output: Contribution to journalReview articlepeer-review

40 Scopus citations

Abstract

Hedgehog (Hh) is first described as a genetic mutation that has “spiked” phenotype in the cuticles of Drosophila in later 1970s. Since then, Hh signaling has been implicated in regulation of differentiation, proliferation, tissue polarity, stem cell population and carcinogenesis. The first link of Hh signaling to cancer was established through discovery of genetic mutations of Hh receptor gene PTCH1 being responsible for Gorlin syndrome in 1996. It was later shown that Hh signaling is associated with many types of cancer, including skin, leukemia, lung, brain and gastrointestinal cancers. Another important milestone for the Hh research field is the FDA approval for the clinical use of Hh inhibitor Erivedge/Vismodegib for treatment of locally advanced and metastatic basal cell carcinomas. However, recent clinical trials of Hh signaling inhibitors in pancreatic, colon and ovarian cancer all failed, indicating a real need for further understanding of Hh signaling in cancer. In this review, we will summarize recent progress in the Hh signaling mechanism and its role in human cancer.

Original languageEnglish (US)
Pages (from-to)179-191
Number of pages13
JournalArchives of Toxicology
Volume89
Issue number2
DOIs
StatePublished - 2015

Keywords

  • Animal model
  • Cancer
  • Clinical trials
  • Hedgehog
  • PTCH1
  • Signal transduction
  • Smoothened

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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