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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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Autores principales: Diaz-Moralli, Santiago, Aguilar, Esther, Marin, Silvia, Coy, Johannes F., Dewerchin, Mieke, Antoniewicz, Maciek R., Meca-Cortés, Oscar, Notebaert, Leen, Ghesquière, Bart, Eelen, Guy, Thomson, Timothy M., Carmeliet, Peter, Cascante, Marta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5239521/
https://www.ncbi.nlm.nih.gov/pubmed/27391434
http://dx.doi.org/10.18632/oncotarget.10429
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author Diaz-Moralli, Santiago
Aguilar, Esther
Marin, Silvia
Coy, Johannes F.
Dewerchin, Mieke
Antoniewicz, Maciek R.
Meca-Cortés, Oscar
Notebaert, Leen
Ghesquière, Bart
Eelen, Guy
Thomson, Timothy M.
Carmeliet, Peter
Cascante, Marta
author_facet Diaz-Moralli, Santiago
Aguilar, Esther
Marin, Silvia
Coy, Johannes F.
Dewerchin, Mieke
Antoniewicz, Maciek R.
Meca-Cortés, Oscar
Notebaert, Leen
Ghesquière, Bart
Eelen, Guy
Thomson, Timothy M.
Carmeliet, Peter
Cascante, Marta
author_sort Diaz-Moralli, Santiago
collection PubMed
description 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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spelling pubmed-52395212017-01-24 A key role for transketolase-like 1 in tumor metabolic reprogramming Diaz-Moralli, Santiago Aguilar, Esther Marin, Silvia Coy, Johannes F. Dewerchin, Mieke Antoniewicz, Maciek R. Meca-Cortés, Oscar Notebaert, Leen Ghesquière, Bart Eelen, Guy Thomson, Timothy M. Carmeliet, Peter Cascante, Marta Oncotarget Research Paper 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. Impact Journals LLC 2016-07-06 /pmc/articles/PMC5239521/ /pubmed/27391434 http://dx.doi.org/10.18632/oncotarget.10429 Text en Copyright: © 2016 Diaz-Moralli et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Diaz-Moralli, Santiago
Aguilar, Esther
Marin, Silvia
Coy, Johannes F.
Dewerchin, Mieke
Antoniewicz, Maciek R.
Meca-Cortés, Oscar
Notebaert, Leen
Ghesquière, Bart
Eelen, Guy
Thomson, Timothy M.
Carmeliet, Peter
Cascante, Marta
A key role for transketolase-like 1 in tumor metabolic reprogramming
title A key role for transketolase-like 1 in tumor metabolic reprogramming
title_full A key role for transketolase-like 1 in tumor metabolic reprogramming
title_fullStr A key role for transketolase-like 1 in tumor metabolic reprogramming
title_full_unstemmed A key role for transketolase-like 1 in tumor metabolic reprogramming
title_short A key role for transketolase-like 1 in tumor metabolic reprogramming
title_sort key role for transketolase-like 1 in tumor metabolic reprogramming
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5239521/
https://www.ncbi.nlm.nih.gov/pubmed/27391434
http://dx.doi.org/10.18632/oncotarget.10429
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