Wong Elaine Yue Ling, Wong Sze-Chuen Cesar, Chan Charles Ming Lok, Lam Emily Kai Yee, Ho Louisa Yeung, Lau Cecilia Pik Yuk, Au Thomas Chi Chuen, Chan Amanda Kit Ching, Tsang Chi Man, Tsao Sai Wah, Lui Vivian Wai Yan, Chan Anthony Tak Cheung
State Key Laboratory of Oncology in South China, Sir YK Pao Centre for Cancer, Department of Clinical Oncology, Hong Kong Cancer Institute and Prince of Wales Hospital, The Chinese University of Hong Kong, P.R. China.
State Key Laboratory of Oncology in South China, Sir YK Pao Centre for Cancer, Department of Clinical Oncology, Hong Kong Cancer Institute and Prince of Wales Hospital, The Chinese University of Hong Kong, P.R. China ; Department of Health Technology and Informatics, Hong Kong Polytechnic University, Hong Kong SAR, P.R. China.
Oncol Lett. 2015 Feb;9(2):569-574. doi: 10.3892/ol.2014.2797. Epub 2014 Dec 12.
The -induced glycolysis and apoptosis regulator (TIGAR) is the protein product of the p53 target gene, . TIGAR blocks glycolysis and promotes cellular metabolism via the pentose phosphate pathway; it promotes the production of cellular nicotinamide adenine dinucleotide phosphate (NADPH), which leads to enhanced scavenging of intracellular reactive oxygen species, and inhibition of oxidative stress-induced apoptosis in normal cells. Our previous study identified a novel nucleoside analog that inhibited cellular growth and induced apoptosis in nasopharyngeal carcinoma (NPC) cell lines via downregulation of TIGAR expression. Furthermore, the growth inhibitory effects of c-Met tyrosine kinase inhibitors were ameliorated by the overexpression of TIGAR in the NPC cell lines. These results indicate a significant role for TIGAR expression in the survival of NPCs. The present study aimed to further define the function of TIGAR expression in NPC cells. In total, 36 formalin-fixed, paraffin-embedded NPC tissue samples were obtained for the immunohistochemical determination of TIGAR expression. The effects of TIGAR expression on cell proliferation, NADPH production and cellular invasiveness were also assessed in NPC cell lines. Overall, TIGAR was overexpressed in 27/36 (75%) of the NPC tissues compared with the adjacent non-cancer epithelial cells. Similarly, TIGAR overexpression was also observed in a panel of six NPC cell lines compared with normal NP460 hTert and Het1A cell lines. TIGAR overexpression led to increased cellular growth, NADPH production and invasiveness of the NPC cell lines, whereas a knockdown of TIGAR expression resulted in significant inhibition of cellular growth and invasiveness. The expression of the two mesenchymal markers, fibronectin and vimentin, was increased by TIGAR overexpression, but reduced following TIGAR-knockdown. The present study revealed that TIGAR overexpression led to increased cellular growth, NADPH production and invasiveness, and the maintenance of a mesenchymal phenotype, in NPC tissues.
p53靶基因诱导的糖酵解和凋亡调节因子（TIGAR）是p53靶基因的蛋白质产物。TIGAR通过磷酸戊糖途径阻断糖酵解并促进细胞代谢；它促进细胞烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的产生，这导致细胞内活性氧的清除增强，并抑制正常细胞中氧化应激诱导的凋亡。我们之前的研究鉴定了一种新型核苷类似物，其通过下调TIGAR表达抑制鼻咽癌细胞系的细胞生长并诱导凋亡。此外，在鼻咽癌细胞系中，TIGAR的过表达改善了c-Met酪氨酸激酶抑制剂的生长抑制作用。这些结果表明TIGAR表达在鼻咽癌的存活中起重要作用。本研究旨在进一步明确TIGAR表达在鼻咽癌细胞中的功能。总共获得了36个福尔马林固定、石蜡包埋的鼻咽癌组织样本，用于免疫组织化学检测TIGAR表达。还在鼻咽癌细胞系中评估了TIGAR表达对细胞增殖、NADPH产生和细胞侵袭性的影响。总体而言，与相邻的非癌上皮细胞相比，27/36（75%）的鼻咽癌组织中TIGAR过表达。同样，与正常NP460 hTert和Het1A细胞系相比，在一组六个鼻咽癌细胞系中也观察到TIGAR过表达。TIGAR过表达导致鼻咽癌细胞系的细胞生长、NADPH产生和侵袭性增加，而TIGAR表达的敲低导致细胞生长和侵袭性的显著抑制。TIGAR过表达增加了两种间充质标志物纤连蛋白和波形蛋白的表达，但在TIGAR敲低后降低。本研究表明，TIGAR过表达导致鼻咽癌组织中细胞生长、NADPH产生和侵袭性增加，并维持间充质表型。
Zotero 插件
