A key role for transketolase-like 1 in tumor metabolic reprogramming
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...
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| Published in | Oncotarget Vol. 7; no. 32; pp. 51875 - 51897 |
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| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Impact Journals LLC
09.08.2016
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1949-2553 1949-2553 |
| DOI | 10.18632/oncotarget.10429 |
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| 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. |
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| AbstractList | 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. |
| Author | Marin, Silvia Ghesquière, Bart Notebaert, Leen Meca-Cortés, Oscar Cascante, Marta Dewerchin, Mieke Diaz-Moralli, Santiago Coy, Johannes F. Thomson, Timothy M. Antoniewicz, Maciek R. Eelen, Guy Aguilar, Esther Carmeliet, Peter |
| AuthorAffiliation | 6 Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, Leuven, Belgium 3 Tavargenix GmbH, Frankfurt am Main, Germany 2 Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain 1 Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain 8 Department of Cell Biology, Institute for Molecular Biology of Barcelona, National Research Council (IBMB-CSIC), Barcelona, Spain 4 Zyagnum AG, Frankfurt am Main, Germany 5 Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium 7 Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, DE, USA |
| AuthorAffiliation_xml | – name: 2 Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain – name: 8 Department of Cell Biology, Institute for Molecular Biology of Barcelona, National Research Council (IBMB-CSIC), Barcelona, Spain – name: 5 Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium – name: 7 Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, DE, USA – name: 3 Tavargenix GmbH, Frankfurt am Main, Germany – name: 4 Zyagnum AG, Frankfurt am Main, Germany – name: 1 Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain – name: 6 Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, Leuven, Belgium |
| Author_xml | – sequence: 1 givenname: Santiago surname: Diaz-Moralli fullname: Diaz-Moralli, Santiago organization: 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 – sequence: 2 givenname: Esther surname: Aguilar fullname: Aguilar, Esther organization: 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 – sequence: 3 givenname: Silvia surname: Marin fullname: Marin, Silvia organization: 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 – sequence: 4 givenname: Johannes F. surname: Coy fullname: Coy, Johannes F. organization: Tavargenix GmbH, Frankfurt am Main, Germany, Zyagnum AG, Frankfurt am Main, Germany – sequence: 5 givenname: Mieke surname: Dewerchin fullname: Dewerchin, Mieke organization: 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 – sequence: 6 givenname: Maciek R. surname: Antoniewicz fullname: Antoniewicz, Maciek R. organization: Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, DE, USA – sequence: 7 givenname: Oscar surname: Meca-Cortés fullname: Meca-Cortés, Oscar organization: Department of Cell Biology, Institute for Molecular Biology of Barcelona, National Research Council (IBMB-CSIC), Barcelona, Spain – sequence: 8 givenname: Leen surname: Notebaert fullname: Notebaert, Leen organization: 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 – sequence: 9 givenname: Bart surname: Ghesquière fullname: Ghesquière, Bart organization: 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 – sequence: 10 givenname: Guy surname: Eelen fullname: Eelen, Guy organization: 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 – sequence: 11 givenname: Timothy M. surname: Thomson fullname: Thomson, Timothy M. organization: Department of Cell Biology, Institute for Molecular Biology of Barcelona, National Research Council (IBMB-CSIC), Barcelona, Spain – sequence: 12 givenname: Peter surname: Carmeliet fullname: Carmeliet, Peter organization: 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 – sequence: 13 givenname: Marta surname: Cascante fullname: Cascante, Marta organization: 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 |
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| Keywords | transketolase-like 1 metabolic reprogramming pentose phosphate pathway tumor metabolism lipid metabolism |
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| Title | A key role for transketolase-like 1 in tumor metabolic reprogramming |
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