TKTL1 promotes cell proliferation and metastasis in esophageal squamous cell carcinoma.
Transketolase-like-1 (TKTL1), which is a rate-limiting enzyme in the non-oxidative part of the pentose-phosphate pathway, has been demonstrated to promote carcinogenesis through enhanced aerobic glycolysis. Dysregulation of TKTL1 expression also leads to poor prognosis in patients with urothelial and colorectal cancer. However, the expression pattern and underlying cellular functions in human esophageal squamous cell carcinoma (ESCC) remain largely unexplored. In this study, we measured TKTL1 expression in ESCC cell lines and paraffin-embedded ESCC tumor tissues. Our results revealed that TKTL1 expression was upregulated in all of the four ESCC cell lines and in 61.25% (98/160) of ESCC specimens detected, while only 27.5% (11/40) in normal epithelium. Silencing of TKTL1 expression decreased cell proliferation through inhibiting the expression of MKI67 and cyclins including Ccna2, Ccnb1, Ccnd1 and Ccne1. Meanwhile, down-regulation of TKTL1 also associated with increased apoptotic ratio and altered protein expression of Bcl-2 family in ESCC cells. Furthermore, knockdown of TKTL1 significantly reduced the invasive potential of ESCC cells through up-regulation of anti-metastasis genes (MTSS1, TIMP2 and CTSK) and down-regulation of pr-metastasis genes (MMP2, MMP9, MMP10 and MMP13). Taken together, our results indicate that TKTL1 is associated with a more aggressive behavior in ESCC cells and suppresses its expression or enzyme activity might represents a potential target for developing novel therapies in human ESCCs.
The Third Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
Juan
J
Li
The Third Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China. Electronic address: sczhu@heinfo.net.
Shu-Chai
SC
Zhu
The Third Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
Shu-Guang
SG
Li
The Third Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
Yan
Y
Zhao
The Third Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
Jin-Rui
JR
Xu
The Third Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
Chun-Yang
CY
Song
D017209:Apoptosis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D014174:Transketolase / Q000235:genetics*; D015854:Up-Regulation
C505431:TKTL1 protein, human; D014174:Transketolase
Esophageal squamous cell carcinoma; Metastasis; Proliferation; TKTL