Hedgehog signaling activation in the development of squamous cell carcinoma and adenocarcinoma of esophagus

Ling Yang, Li Shu Wang, Xiaoxin(Luke) Chen, Zoran Gatalica, Suimin Qiu, Zhihua Liu, Gary Stoner, Hongwei Zhang, Heidi Weiss, Jingwu Xie

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Hedgehog (Hh) signaling is frequently activated in human cancer, including esophageal cancer. Most esophageal cancers are diagnosed in the advanced stages, therefore, identifying the very alterations that drive esophageal carcinogenesis may help designing novel strategies to diagnose and treat the disease. Analysis of Hh signaling in precancerous lesions is a critical first step in determining the significance of this pathway for carcinogenesis. Here we report our data on Hh target gene expression in 174 human esophageal specimens [28 esophageal adenocarcinomas (EAC), 19 Barrett's esophagus, 103 cases of esophageal squamous cell carcinoma (ESCC), and 24 of squamous dysplastic lesions], and in two rat models of esophageal cancer. We found that 96% of human EAC express Hh target genes. We showed that PTCH1 expression is the most reliable biomarker. In contrast to EAC, only 38% of ESCC ex- press Hh target genes. We found activation of Hh signaling in precancerous lesions of ESCCs and EACs in different degrees (21% and 58% respectively). Expression of Hh target genes is frequently detected in severe squamous dys- plasia/ carcinoma in situ (p=0.04) and Barrett's esophagus (p=0.01). Unlike EAC, sonic hedgehog (Shh) expression was rare in ESCCs. Consistent with the human specimen data, we found a high percentage of Hh signaling activation in precancerous lesions in rat models. These data indicate that Hh signaling activation is an early molecular event in the development of esophageal cancer, particularly EAC.

Original languageEnglish (US)
Pages (from-to)46-57
Number of pages12
JournalInternational Journal of Biochemistry and Molecular Biology
Issue number1
StatePublished - 2012


  • Barrett's esophagus (BE)
  • Esophageal adenocarcinoma (EAC)
  • Esophageal squamous cell carcinoma (ESCC)
  • Gli2
  • Hedgehog (Hh)
  • Human homologue of hedgehog-interaction protein (HHIP)
  • Patched -1 (PTCH1 for humans and ptch1 for animals)
  • Rat model
  • sFRP-1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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