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

TitleTP53-induced glycolysis and apoptosis regulator promotes proliferation and invasiveness of nasopharyngeal carcinoma cells
Authors
Issue Date2015
PublisherSpandidos Publications. The Journal's web site is located at http://www.spandidos-publications.com/ol
Citation
Oncology Letters, 2015, v. 9 n. 2, p. 569-574 How to Cite?
AbstractThe TP53induced 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 stressinduced 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 cMet 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 formalinfixed, paraffinembedded 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 noncancer 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 TIGARknockdown. 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.
Persistent Identifierhttp://hdl.handle.net/10722/213800
ISSN
2015 Impact Factor: 1.482
2015 SCImago Journal Rankings: 0.626
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, EYL-
dc.contributor.authorWong, SCC-
dc.contributor.authorChan, CML-
dc.contributor.authorLam, EKY-
dc.contributor.authorHo, LY-
dc.contributor.authorLau, CPY-
dc.contributor.authorAu, TCC-
dc.contributor.authorChan, AKC-
dc.contributor.authorTsang, CM-
dc.contributor.authorTsao, GSW-
dc.contributor.authorLui, VWY-
dc.contributor.authorChan, ATC-
dc.date.accessioned2015-08-18T07:15:08Z-
dc.date.available2015-08-18T07:15:08Z-
dc.date.issued2015-
dc.identifier.citationOncology Letters, 2015, v. 9 n. 2, p. 569-574-
dc.identifier.issn1792-1074-
dc.identifier.urihttp://hdl.handle.net/10722/213800-
dc.description.abstractThe TP53induced 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 stressinduced 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 cMet 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 formalinfixed, paraffinembedded 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 noncancer 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 TIGARknockdown. 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.-
dc.languageeng-
dc.publisherSpandidos Publications. The Journal's web site is located at http://www.spandidos-publications.com/ol-
dc.relation.ispartofOncology Letters-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleTP53-induced glycolysis and apoptosis regulator promotes proliferation and invasiveness of nasopharyngeal carcinoma cells-
dc.typeArticle-
dc.identifier.emailLau, CPY: cpylau@hkucc.hku.hk-
dc.identifier.emailTsang, CM: annatsan@hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.emailLui, VWY: vlui002@hku.hk-
dc.identifier.authorityTsang, CM=rp01964-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.authorityLui, VWY=rp01876-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3892/ol.2014.2797-
dc.identifier.pmid25621025-
dc.identifier.pmcidPMC4301475-
dc.identifier.scopuseid_2-s2.0-84918816294-
dc.identifier.hkuros246489-
dc.identifier.volume9-
dc.identifier.issue2-
dc.identifier.spage569-
dc.identifier.epage574-
dc.identifier.isiWOS:000349506300009-
dc.publisher.placeGreece-

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