Overexpression of transketolase protein TKTL1 is associated with occurrence and progression in nasopharyngeal carcinoma: a potential therapeutic target in nasopharyngeal carcinoma.
Over 80 years ago, Warburg identified a particular metabolic pathway in carcinomas characterised by the anaerobic degradation of glucose even in the presence of oxygen that leads to the production of large amounts of lactate (known as the Warburg effect). Now, widespread clinical use of positron-emission tomography (PET) has confirmed that there exists enhanced glucose degradation in tumors. Recent research demonstrated that pentose phosphate pathway (PPP) was augmented in some tumors, especially non-oxidative part of PPP. The non-oxidative part of PPP is controlled by transketolase enzyme reactions. The present study designed to evaluate the effect of transketolase activity on nasopharyngeal carcinoma. It was found that the transketolase activity was significantly stronger in human nasopharyngeal carcinoma tissues than those in human chronic nasopharyngitis tissues. There is a strong upregulation of the transketolase-like-1 (TKTL1) in human nasopharyngeal carcinoma tissues and cell line (CNE), whereas transketolase (TKT) and transketolase-like-2 (TKTL2) were not upregulated. After inhibited the expression of (TKTL1) by RNAi, we found that total transketolase activity was dramatically downregulated and the proliferation of cancer cells was significantly inhibited in CNE cells. These results indicate that TKTL1 gene influences total transketolase activity and cell proliferation in human nasopharyngeal carcinoma cells, suggesting that TKTL1 gene plays an important role on glycometabolism in tumors and it might become a novel target for tumor gene therapy.
Zhang
Song
S
Department of Otolaryngology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Yue
Jian Xin
JX
Yang
Ju Hong
JH
Cai
Peng Cheng
PC
Kong
Wei Jia
WJ
D002277:Carcinoma / Q000201:enzymology* / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology* / Q000628:therapy*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D014174:Transketolase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D012333:RNA, Messenger; D034741:RNA, Small Interfering; C505431:TKTL1 protein, human; D014174:Transketolase