TP53-induced glycolysis and apoptosis regulator promotes proliferation and invasiveness of nasopharyngeal carcinoma cells

Elaine Yue Ling Wong, Sze Chuen Cesar Wong, Charles Ming Lok Chan, Emily Kai Yee Lam, Louisa Yeung Ho, Cecilia Pik Yuk Lau, Thomas Chi Chuen Au, Amanda Kit Ching Chan, Chi Man Tsang, Sai Wah Tsao, Vivian Wai Yan Lui, Anthony Tak Cheung Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

22 Citations (Scopus)


The TP53-induced glycolysis and apoptosis regulator (TIGAR) is the protein product of the p53 target gene, C12orf5. 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.
Original languageEnglish
Pages (from-to)569-574
Number of pages6
JournalOncology Letters
Issue number2
Publication statusPublished - 1 Feb 2015


  • Cell growth
  • Invasiveness
  • Mesenchymal
  • Nasopharyngeal carcinoma
  • TP53-induced glycolysis and apoptosis regulator

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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