title: TKTL1 expression and its downregulation is implicated in cell proliferation inhibition and cell cycle arrest in esophageal squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, Henan, People's Republic of China.|Department of Oncology, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, People's Republic of China.
authors.forename: Zuxuan
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Critical Care Medicine, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Oncology, The Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, Henan, People's Republic of China. fanqingxia2011@126.com.
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Fan
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008875:Middle Aged; D011379:Prognosis; D014174:Transketolase / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C505431:TKTL1 protein, human; D014174:Transketolase
keywords: Cell cycle; Cell proliferation; Esophageal squamous cell carcinoma; Prognosis; Transketolase-like 1