Transketolase serves a poor prognosticator in esophageal cancer by promoting cell invasion via epithelial-mesenchymal transition

Yin Kai Chao, Ta Lun Peng, Wen Yu Chuang, Chi Ju Yeh, Yan Liang Li, Ya Ching Lu, Ann Joy Cheng*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

14 Scopus citations

Abstract

Background: To characterize the potential function and clinical significance of Transketolase (TKT) in esophageal cancer. Methods: High invasive esophageal squamous cell carcinoma (ESCC) cell line CE48T/VGH was used. Cellular functions in response to TKT modulation were examined, including cell growth, migration and invasion. The underlying molecules involved in the TKT regulatory mechanism were determined by western blot and confocal microscopic analysis. Clinically, TKT expressions in 76 ESCC patients were assessed by immunohistochemical (IHC) method, and the association with treatment outcome was determined. Results: TKT silencing inhibited cell migration and invasion but had a minimal effect on cell growth. This TKT silencing also induced the reversion of epithelial-mesenchymal transition (EMT), as evidenced by the spindle to cuboidal morphological change, increased the expression of epithelial markers (?-catenin), and decreased the levels of mesenchymal markers (fibronectin and N-cadherin). Mechanically, TKT was shown to modulate the EMT through the pERK-Slug/Snail-associated signaling pathway. Clinically, a high level of TKT in the cancer tissues of patients with esophageal squamous cell carcinoma was associated with poor survival (P = 0.042). In the multivariate analysis, a high TKT level was also shown to be an independent unfavorable prognostic factor (Odds ratio: 1.827, 95% confidence interval: 1.045-3.196, P = 0.035). Conclusions: TKT contributes to esophageal cancer by promoting cell invasion via meditating EMT process. Clinically, the over-expression of TKT in ESCC patients predicts poorer survival. TKT inhibition may be a useful strategy to intervene in cancer cell invasion and metastasis, which may lead to better prognosis for ESCC patients.

Original languageEnglish
Pages (from-to)1804-1811
Number of pages8
JournalJournal of Cancer
Volume7
Issue number13
DOIs
StatePublished - 2016

Bibliographical note

Publisher Copyright:
© Ivyspring International Publisher.

Keywords

  • Cell invasion
  • Epithelial-mesenchymal transition
  • Esophageal cancer
  • Prognosis
  • Transketolase

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