Exogenous expression of Esophagin/SPRR3 attenuates the tumorigenicity of esophageal squamous cell carcinoma cells via promoting apoptosis

Yu Zhang, Yan Bin Feng, Xiao Ming Shen, Bao Sheng Chen, Xiao Li Du, Man Li Luo, Yan Cai, Ya Ling Han, Xin Xu, Qi Min Zhan, Ming Rong Wang

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Esophagin/SPRR3 is one of the cornified-envelope structural precursor proteins, which is expressed during epithelia cell differentiation. In 1996, another research group discovered, and our own laboratory subsequently confirmed, frequent and dramatic decreased Esophagin/SPRR3 expression in esophageal squamous cell carcinoma (ESCC). However, the role of Esophagin/SPRR3 in tumorigenesis of esophageal epithelium remains undetermined. In this study, we demonstrate that expression of Esophagin/SPRR3 is frequently downregulated in ESCC. In contrast, no correlations between downregulation of Esophagin/SPRR3 expression and clinicopathologic characteristics were observed. Diminished Esophagin/SPRR3 expression was present in dysplastic epithelia, suggesting that Esophagin/SPRR3 alteration could represent an early event in squamous carcinogenesis of the esophagus. Exogenous expression of Esophagin/SPRR3 significantly suppressed the ability of ESCC cells to form colonies in plastic and soft agar, as well as tumor formation in vivo. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end label assay and immunofluorescence analysis of the active form of Caspase 3 indicated that dysregulated apoptosis might contribute to reduced tumorigenicity. In particular, upregulation of CDK11p46 protein was observed in ESCC cells expressing Esophagin/SPRR3, but not in control cells, indicating that Esophagin/SPRR3-induced apoptosis may be due, at least in part, to increased expression of CDK11p46 protein. These findings suggest that Esophagin/SPRR3 may play a role in the maintenance of normal esophageal epithelial homeostasis, and that aberrant expression of Esophagin/SPRR3 may contribute to the tumorigenesisof ESCC.

Original languageEnglish
Pages (from-to)260-266
Number of pages7
JournalInternational Journal of Cancer
Volume122
Issue number2
DOIs
StatePublished - Jan 15 2008
Externally publishedYes

Keywords

  • Apoptosis
  • ESCC
  • Esophagin/SPRR3
  • Tumorigenicity

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