TKTL1 expression and its downregulation is implicated in cell proliferation inhibition and cell cycle arrest in esophageal squamous cell carcinoma
- 194 Downloads
It is well known that tumor cells mainly depend on the nonoxidative pathway of the pentose phosphate pathway (PPP), and transketolase-like 1 (TKTL1), a kind of crucial metabolism enzyme, participates in the regulation of PPP; notably, overwhelming evidence has demonstrated that TKTL1 plays pivotal roles in the development and progression of multiple tumors. However, there were no reports about the role of TKTL1 in esophageal squamous cell carcinoma (ESCC). Here, we investigated TKTL1 expression and preliminarily elucidated its underlying biological functions in ESCC. We found that TKTL1 exhibited the high expression in ESCC tissues and cells, and the survival rate of patients with negative TKTL1 expression was significantly higher than that of patients with positive TKTL1 staining (P < 0.05). Additionally, significant correlations of TKTL1 expression with histologic grade, clinical stage, and lymph node metastasis were found (P < 0.05). Subsequently, TKTL1 small interfering RNA (siRNA) significantly reduced TKTL1 messenger RNA (mRNA), and protein levels companied with the marked reduce of total transketolase activity but did not affect TKT and TKTL1 mRNA level. More importantly, TKTL1 siRNA obviously induced cell cycle arrest in G0/G1 phase and suppressed cell proliferation in vitro and in vivo coupled with the reduced cyclin D1 and cdk4 levels as well as decrease of Ki-67 proliferation index in EC1 cells. Taken altogether, our results suggest that TKTL1 as a key prognostic factor may be a novel target for therapy of the patients with ESCC.
KeywordsTransketolase-like 1 Esophageal squamous cell carcinoma Prognosis Cell proliferation Cell cycle
- 14.Semilia M, Hennenlotter J, Pavone C, Bischoff T, Kuhs U, Gakis G, Bedke J, Stenzl A, Schwentner C, Todenhofer T: Expression patterns and prognostic role of transketolase-like 1 in muscle-invasive bladder cancer. World J Urol 2015. In pressGoogle Scholar
- 28.Wittig R, Coy JF. The role of glucose metabolism and glucose-associated signalling in cancer. Perspect Med Chem. 2008;1:64–82.Google Scholar
- 36.Schwaab J, Horisberger K, Strobel P, Bohn B, Gencer D, Kahler G, et al. Expression of Transketolase like gene 1 (TKTL1) predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy. BMC Cancer. 2011;11:363.CrossRefPubMedPubMedCentralGoogle Scholar