Overexpression of transketolase protein TKTL1 is associated with occurrence and progression in nasopharyngeal carcinoma (Retracted Article. See vol 10, pg 110, 2010)
Overexpression of transketolase protein TKTL1 is associated with occurrence and progression in nasopharyngeal carcinoma (Retracted Article. See vol 10, pg 110, 2010)
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DOI：
10.4161/cbt.7.4.5479
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发表时间：
2008-04-01
影响因子：
3.6
通讯作者：
Kong, Wei Jia
中科院分区：
文献类型：
--
作者：
Zhang, Song;Yue, Jian Xin;Kong, Wei Jia
80多年前，瓦尔堡在癌症中发现了一种特殊的代谢途径，其特征是即使在氧气存在下葡萄糖的厌氧降解，导致产生大量乳酸（称为瓦尔堡效应）。目前，正电子发射断层扫描（PET）的广泛临床应用证实了肿瘤中存在葡萄糖降解增强。近年来的研究表明，磷酸戊糖途径（PPP）在某些肿瘤中增强，尤其是PPP的非氧化部分。PPP的非氧化部分由转酮醇酶反应控制。本研究旨在探讨转酮醇酶活性对鼻咽癌的影响。结果发现，人鼻咽癌组织中的转酮醇酶活性明显强于人慢性鼻咽炎组织。在人鼻咽癌组织和细胞系（CNE）中，转酮醇酶样1（transketolase-like-1，TKTL 1）表达明显上调，而转酮醇酶（transketolase，TKT）和转酮醇酶样2（transketolase-like-2，TKTL 2）表达不上调。在CNE细胞中，通过RNAi抑制TKTL 1的表达后，我们发现总转酮醇酶活性显著下调，并且癌细胞的增殖受到显著抑制。这些结果表明，TKTL 1基因影响人鼻咽癌细胞的总转酮醇酶活性和细胞增殖，提示TKTL 1基因在肿瘤糖代谢中起重要作用，可能成为肿瘤基因治疗的新靶点。
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.