J Cancer 2016; 7(13):1804-1811. doi:10.7150/jca.15467 This issue
1. Division of Thoracic Surgery, Chang Gung Memorial Hospital-Linko, Chang Gung University, Taoyuan 333, Taiwan;
2. Department of Medical Biotechnology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
3. Department of Pathology, Chang Gung Memorial Hospital-Linko, Chang Gung University, Taoyuan 333, Taiwan.
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 (γ-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.
Keywords: transketolase, esophageal cancer, prognosis, cell invasion, epithelial-mesenchymal transition.