Oncotarget

Research Papers:

A key role for transketolase-like 1 in tumor metabolic reprogramming

Santiago Diaz-Moralli, Esther Aguilar, Silvia Marin, Johannes F. Coy, Mieke Dewerchin, Maciek R. Antoniewicz, Oscar Meca-Cortés, Leen Notebaert, Bart Ghesquière, Guy Eelen, Timothy M. Thomson, Peter Carmeliet and Marta Cascante _

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Oncotarget. 2016; 7:51875-51897. https://doi.org/10.18632/oncotarget.10429

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Abstract

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

Correspondence to:

Marta Cascante, email: martacascante@ub.edu

Peter Carmeliet, email: peter.carmeliet@vib-kuleuven.be

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

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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