title: TP53-induced glycolysis and apoptosis regulator promotes proliferation and invasiveness of nasopharyngeal carcinoma cells.
abstract: TheTP53-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.
authors.affiliation: 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.
authors.forename: Elaine Yue Ling
authors.initials: EY
authors.lastname: Wong
authors.affiliation: 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.
authors.forename: Sze-Chuen Cesar
authors.initials: SC
authors.lastname: Wong
authors.affiliation: 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.
authors.forename: Charles Ming Lok
authors.initials: CM
authors.lastname: Chan
authors.affiliation: 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.
authors.forename: Emily Kai Yee
authors.initials: EK
authors.lastname: Lam
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Louisa Yeung
authors.initials: LY
authors.lastname: Ho
authors.affiliation: 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.
authors.forename: Cecilia Pik Yuk
authors.initials: CP
authors.lastname: Lau
authors.affiliation: 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.
authors.forename: Thomas Chi Chuen
authors.initials: TC
authors.lastname: Au
authors.affiliation: Department of Pathology, Queen Elizabeth Hospital, University of Hong Kong, Hong Kong SAR, P.R. China.
authors.forename: Amanda Kit Ching
authors.initials: AK
authors.lastname: Chan
authors.affiliation: Department of Anatomy, University of Hong Kong, Hong Kong SAR, P.R. China.
authors.forename: Chi Man
authors.initials: CM
authors.lastname: Tsang
authors.affiliation: Department of Anatomy, University of Hong Kong, Hong Kong SAR, P.R. China.
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
authors.affiliation: Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong SAR, P.R. China.
authors.forename: Vivian Wai Yan
authors.initials: VW
authors.lastname: Lui
authors.affiliation: 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.
authors.forename: Anthony Tak Cheung
authors.initials: AT
authors.lastname: Chan
keywords: TP53-induced glycolysis and apoptosis regulator; cell growth; invasiveness; mesenchymal; nasopharyngeal carcinoma