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

107 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Esophageal Neoplasms
Neoplasms
Apoptosis
Genes
Growth
Neutralizing Antibodies
Down-Regulation
3-keto-N-aminoethylaminoethylcaproyldihydrocinnamoyl cyclopamine

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hedgehog signaling is activated in subsets of esophageal cancers. / Ma, Xiaoli; Sheng, Tao; Zhang, Yuanxin; Zhang, Xiaoli; He, Jing; Huang, Shuhong; Chen, Kai; Sultz, Josh; Adegboyega, Patrick A.; Zhang, Hongwei; Xie, Jingwu.

In: International Journal of Cancer, Vol. 118, No. 1, 01.01.2006, p. 139-148.

Research output: Contribution to journalArticle

Ma, X, Sheng, T, Zhang, Y, Zhang, X, He, J, Huang, S, Chen, K, Sultz, J, Adegboyega, PA, Zhang, H & Xie, J 2006, 'Hedgehog signaling is activated in subsets of esophageal cancers', International Journal of Cancer, vol. 118, no. 1, pp. 139-148. https://doi.org/10.1002/ijc.21295
Ma, Xiaoli ; Sheng, Tao ; Zhang, Yuanxin ; Zhang, Xiaoli ; He, Jing ; Huang, Shuhong ; Chen, Kai ; Sultz, Josh ; Adegboyega, Patrick A. ; Zhang, Hongwei ; Xie, Jingwu. / Hedgehog signaling is activated in subsets of esophageal cancers. In: International Journal of Cancer. 2006 ; Vol. 118, No. 1. pp. 139-148.
@article{2e81485008ab4e0a86f24be4fe26d042,
title = "Hedgehog signaling is activated in subsets of esophageal cancers",
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).",
keywords = "Cyclopamine, Esophageal cancer, GI cancer, Smoothened, Sonic hedgehog",
author = "Xiaoli Ma and Tao Sheng and Yuanxin Zhang and Xiaoli Zhang and Jing He and Shuhong Huang and Kai Chen and Josh Sultz and Adegboyega, {Patrick A.} and Hongwei Zhang and Jingwu Xie",
year = "2006",
month = "1",
day = "1",
doi = "10.1002/ijc.21295",
language = "English (US)",
volume = "118",
pages = "139--148",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Hedgehog signaling is activated in subsets of esophageal cancers

AU - Ma, Xiaoli

AU - Sheng, Tao

AU - Zhang, Yuanxin

AU - Zhang, Xiaoli

AU - He, Jing

AU - Huang, Shuhong

AU - Chen, Kai

AU - Sultz, Josh

AU - Adegboyega, Patrick A.

AU - Zhang, Hongwei

AU - Xie, Jingwu

PY - 2006/1/1

Y1 - 2006/1/1

N2 - 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).

AB - 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).

KW - Cyclopamine

KW - Esophageal cancer

KW - GI cancer

KW - Smoothened

KW - Sonic hedgehog

UR - http://www.scopus.com/inward/record.url?scp=27944470037&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27944470037&partnerID=8YFLogxK

U2 - 10.1002/ijc.21295

DO - 10.1002/ijc.21295

M3 - Article

VL - 118

SP - 139

EP - 148

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 1

ER -