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

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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.

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Acknowledgments

Current research in my laboratory is supported by grants from the National Cancer Institute CA155086, Riley Children’s Foundation and Wells Center for Pediatric Research. Due to space limit, we could not include many important findings in this review but want to take this opportunity to thank all the investigators in this field for their works.

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Authors and Affiliations

  1. Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, China

    Yanfei Jia & Yunshan Wang

  2. Division of Hematology and Oncology, Department of Pediatrics, Wells Center for Pediatric Research, Indiana University Simon Cancer Center, Indiana University, Indianapolis, IN, 46202, USA

    Yanfei Jia & Jingwu Xie

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Jia, Y., Wang, Y. & Xie, J. The Hedgehog pathway: role in cell differentiation, polarity and proliferation. Arch Toxicol 89, 179–191 (2015). https://doi.org/10.1007/s00204-014-1433-1

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