title: Akt mediates TIGAR induction in HeLa cells following PFKFB3 inhibition.
abstract: Neoplastic cells metabolize higher amounts of glucose relative to normal cells in order to cover increased energetic and anabolic needs. Inhibition of the glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) diminishes cancer cell proliferation and tumour growth in animals. In this work, we investigate the crosstalk between PFKFB3 and TIGAR (TP53-Induced Glycolysis and Apoptosis Regulator), a protein known to protect cells from oxidative stress. Our results show consistent TIGAR induction in HeLa cells in response to PFKFB3 knockdown. Upon PFKFB3 silencing, cells undergo oxidative stress and trigger Akt phosphorylation. This leads to induction of a TIGAR-mediated prosurvival pathway that reduces both oxidative stress and cell death. As TIGAR is known to have a role in DNA repair, it could serve as a potential target for the development of effective antineoplastic therapies.
authors.affiliation: Unitat de Bioquímica, Departament de Ciències Fisiològiques, IDIBELL-Universitat de Barcelona, Spain.
authors.forename: Helga
authors.initials: H
authors.lastname: Simon-Molas
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: María Nieves
authors.initials: MN
authors.lastname: Calvo-Vidal
authors.affiliation: Centres Científics i Tecnològics, IDIBELL-Universitat de Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Castaño
authors.affiliation: Unitat de Bioquímica, Departament de Ciències Fisiològiques, IDIBELL-Universitat de Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Rodríguez-García
authors.affiliation: Unitat de Bioquímica, Departament de Ciències Fisiològiques, IDIBELL-Universitat de Barcelona, Spain.
authors.forename: Àurea
authors.initials: À
authors.lastname: Navarro-Sabaté
authors.affiliation: Unitat de Bioquímica, Departament de Ciències Fisiològiques, IDIBELL-Universitat de Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Bartrons
authors.affiliation: Unitat de Bioquímica, Departament de Ciències Fisiològiques, IDIBELL-Universitat de Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Manzano
mesh_terms: D051017:Apoptosis Regulatory Proteins; D049109:Cell Proliferation / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics*; D025481:Phosphofructokinase-2 / Q000096:biosynthesis* / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; C107345:PFKFB3 protein, human; D025481:Phosphofructokinase-2; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; C512708:TIGAR protein, human
keywords: Akt; PFKFB3; TIGAR; glycolysis; tumour cell metabolism