title: A key role for transketolase-like 1 in tumor metabolic reprogramming.
abstract: Metabolic reprogramming, a crucial cancer hallmark, shifts metabolic pathways such as glycolysis, tricarboxylic acid cycle or lipogenesis, to enable the growth characteristics of cancer cells. Here, we provide evidence that transketolase-like 1 (TKTL1) orchestrates aerobic glycolysis, fatty acid and nucleic acid synthesis, glutamine metabolism, protection against oxidative stress and cell proliferation. Furthermore, silencing of TKTL1 reduced the levels of sphingolipids such as lactosylceramide (a sphingolipid regulating cell survival, proliferation and angiogenesis) and phosphatidylinositol (which activates PI3K/Akt/mTOR signaling). Thus, in addition to its well-known roles in glucose and amino acid metabolism, TKTL1 also regulates lipid metabolism. In conclusion, our study provides unprecedented evidence that TKTL1 plays central roles in major metabolic processes subject to reprogramming in cancer cells and thus identifies TKTL1 as a promising target for new anti-cancer therapies.
authors.affiliation: Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Diaz-Moralli
authors.affiliation: Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Aguilar
authors.affiliation: Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Marin
authors.affiliation: Tavargenix GmbH, Frankfurt am Main, Germany.|Zyagnum AG, Frankfurt am Main, Germany.
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Coy
authors.affiliation: Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium.|Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, Leuven, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.affiliation: Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, DE, USA.
authors.forename: Maciek R
authors.initials: MR
authors.lastname: Antoniewicz
authors.affiliation: Department of Cell Biology, Institute for Molecular Biology of Barcelona, National Research Council (IBMB-CSIC), Barcelona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Meca-Cortés
authors.affiliation: Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium.|Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, Leuven, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Notebaert
authors.affiliation: Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium.|Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Ghesquière
authors.affiliation: Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium.|Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Eelen
authors.affiliation: Department of Cell Biology, Institute for Molecular Biology of Barcelona, National Research Council (IBMB-CSIC), Barcelona, Spain.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Thomson
authors.affiliation: Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium.|Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.affiliation: Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Cascante
mesh_terms: D045744:Cell Line, Tumor; D006019:Glycolysis; D006801:Humans; D055442:Metabolome; D009369:Neoplasms / Q000378:metabolism*; D014174:Transketolase / Q000378:metabolism*
chemical_list: C505431:TKTL1 protein, human; D014174:Transketolase
keywords: lipid metabolism; metabolic reprogramming; pentose phosphate pathway; transketolase-like 1; tumor metabolism