Hedgehog signaling is activated in subsets of esophageal cancers

Xiaoli Ma, Tao Sheng, Yuanxin Zhang, Xiaoli Zhang, Jing He, Shuhong Huang, Kai Chen, Josh Sultz, Patrick A. Adegboyega, Hongwei Zhang, Jingwu Xie

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

The hedgehog pathway plays a critical role in the development of the foregut. However, the role of the hedgehog pathway in primary esophageal cancers is not well studied. Here, we report that elevated expression of hedgehog target genes occurs in 14 of 22 primary esophageal cancers. The hedgehog signaling activation is not associated with tumor subtypes, stages, or differentiation. While the sonic hedgehog (Shh) transcript is localized to the tumor tissue, expression of Gli1 and PTCH1 is observed both in the tumor and in the stroma. We discovered that 4 esophageal squamous cell carcinomas, which overexpress Shh, have genomic amplification of the Shh gene. Treatment of esophageal cancer cells with smoothened antagonist, KAAD-cyclopamine, or the neutralizing antibodies of Shh reduces cell growth and induces apoptosis. Overexpression of Gli1 under the CMV promoter renders these cells resistant to the treatments. Thus, our results indicate that elevated expression of Shh and its target genes is quite common in esophageal cancers. Our data also indicate that downregulation of Gli1 expression may be an important mechanism by which KAAD-cyclopamine inhibits growth and induces apoptosis in esophageal cancer cells (supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020- 7136/suppmat/index.html).

Original languageEnglish (US)
Pages (from-to)139-148
Number of pages10
JournalInternational Journal of Cancer
Volume118
Issue number1
DOIs
StatePublished - Jan 1 2006

Keywords

  • Cyclopamine
  • Esophageal cancer
  • GI cancer
  • Smoothened
  • Sonic hedgehog

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Ma, X., Sheng, T., Zhang, Y., Zhang, X., He, J., Huang, S., Chen, K., Sultz, J., Adegboyega, P. A., Zhang, H., & Xie, J. (2006). Hedgehog signaling is activated in subsets of esophageal cancers. International Journal of Cancer, 118(1), 139-148. https://doi.org/10.1002/ijc.21295