A key role for transketolase-like 1 in tumor metabolic reprogramming
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Santiago Diaz-Moralli1,2, Esther Aguilar1,2, Silvia Marin1,2, Johannes F. Coy3,4, Mieke Dewerchin5,6, Maciek R. Antoniewicz7, Oscar Meca-Cortés8, Leen Notebaert5,6, Bart Ghesquière5,6, Guy Eelen5,6, Timothy M. Thomson8, Peter Carmeliet5,6, Marta Cascante1,2
1Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain
2Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain
3Tavargenix GmbH, Frankfurt am Main, Germany
4Zyagnum AG, Frankfurt am Main, Germany
5Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium
6Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, Leuven, Belgium
7Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, DE, USA
8Department of Cell Biology, Institute for Molecular Biology of Barcelona, National Research Council (IBMB-CSIC), Barcelona, Spain
Marta Cascante, email: [email protected]
Peter Carmeliet, email: [email protected]
Keywords: tumor metabolism, metabolic reprogramming, transketolase-like 1, lipid metabolism, pentose phosphate pathway
Received: March 15, 2016 Accepted: June 13, 2016 Published: July 06, 2016
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.
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