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Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt

Cancer metabolism is characterized by an accelerated glycolytic rate facing reduced activity of oxidative phosphorylation. This “Warburg effect” represents a standard to diagnose and monitor tumor aggressiveness with (18)F-fluorodeoxyglucose whose uptake is currently regarded as an accurate index of...

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Autores principales: Marini, Cecilia, Ravera, Silvia, Buschiazzo, Ambra, Bianchi, Giovanna, Orengo, Anna Maria, Bruno, Silvia, Bottoni, Gianluca, Emionite, Laura, Pastorino, Fabio, Monteverde, Elena, Garaboldi, Lucia, Martella, Roberto, Salani, Barbara, Maggi, Davide, Ponzoni, Mirco, Fais, Franco, Raffaghello, Lizzia, Sambuceti, Gianmario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848551/
https://www.ncbi.nlm.nih.gov/pubmed/27121192
http://dx.doi.org/10.1038/srep25092
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author Marini, Cecilia
Ravera, Silvia
Buschiazzo, Ambra
Bianchi, Giovanna
Orengo, Anna Maria
Bruno, Silvia
Bottoni, Gianluca
Emionite, Laura
Pastorino, Fabio
Monteverde, Elena
Garaboldi, Lucia
Martella, Roberto
Salani, Barbara
Maggi, Davide
Ponzoni, Mirco
Fais, Franco
Raffaghello, Lizzia
Sambuceti, Gianmario
author_facet Marini, Cecilia
Ravera, Silvia
Buschiazzo, Ambra
Bianchi, Giovanna
Orengo, Anna Maria
Bruno, Silvia
Bottoni, Gianluca
Emionite, Laura
Pastorino, Fabio
Monteverde, Elena
Garaboldi, Lucia
Martella, Roberto
Salani, Barbara
Maggi, Davide
Ponzoni, Mirco
Fais, Franco
Raffaghello, Lizzia
Sambuceti, Gianmario
author_sort Marini, Cecilia
collection PubMed
description Cancer metabolism is characterized by an accelerated glycolytic rate facing reduced activity of oxidative phosphorylation. This “Warburg effect” represents a standard to diagnose and monitor tumor aggressiveness with (18)F-fluorodeoxyglucose whose uptake is currently regarded as an accurate index of total glucose consumption. Studying cancer metabolic response to respiratory chain inhibition by metformin, we repeatedly observed a reduction of tracer uptake facing a marked increase in glucose consumption. This puzzling discordance brought us to discover that (18)F-fluorodeoxyglucose preferentially accumulates within endoplasmic reticulum by exploiting the catalytic function of hexose-6-phosphate-dehydrogenase. Silencing enzyme expression and activity decreased both tracer uptake and glucose consumption, caused severe energy depletion and decreased NADPH content without altering mitochondrial function. These data document the existence of an unknown glucose metabolism triggered by hexose-6-phosphate-dehydrogenase within endoplasmic reticulum of cancer cells. Besides its basic relevance, this finding can improve clinical cancer diagnosis and might represent potential target for therapy.
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spelling pubmed-48485512016-05-05 Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt Marini, Cecilia Ravera, Silvia Buschiazzo, Ambra Bianchi, Giovanna Orengo, Anna Maria Bruno, Silvia Bottoni, Gianluca Emionite, Laura Pastorino, Fabio Monteverde, Elena Garaboldi, Lucia Martella, Roberto Salani, Barbara Maggi, Davide Ponzoni, Mirco Fais, Franco Raffaghello, Lizzia Sambuceti, Gianmario Sci Rep Article Cancer metabolism is characterized by an accelerated glycolytic rate facing reduced activity of oxidative phosphorylation. This “Warburg effect” represents a standard to diagnose and monitor tumor aggressiveness with (18)F-fluorodeoxyglucose whose uptake is currently regarded as an accurate index of total glucose consumption. Studying cancer metabolic response to respiratory chain inhibition by metformin, we repeatedly observed a reduction of tracer uptake facing a marked increase in glucose consumption. This puzzling discordance brought us to discover that (18)F-fluorodeoxyglucose preferentially accumulates within endoplasmic reticulum by exploiting the catalytic function of hexose-6-phosphate-dehydrogenase. Silencing enzyme expression and activity decreased both tracer uptake and glucose consumption, caused severe energy depletion and decreased NADPH content without altering mitochondrial function. These data document the existence of an unknown glucose metabolism triggered by hexose-6-phosphate-dehydrogenase within endoplasmic reticulum of cancer cells. Besides its basic relevance, this finding can improve clinical cancer diagnosis and might represent potential target for therapy. Nature Publishing Group 2016-04-28 /pmc/articles/PMC4848551/ /pubmed/27121192 http://dx.doi.org/10.1038/srep25092 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Marini, Cecilia
Ravera, Silvia
Buschiazzo, Ambra
Bianchi, Giovanna
Orengo, Anna Maria
Bruno, Silvia
Bottoni, Gianluca
Emionite, Laura
Pastorino, Fabio
Monteverde, Elena
Garaboldi, Lucia
Martella, Roberto
Salani, Barbara
Maggi, Davide
Ponzoni, Mirco
Fais, Franco
Raffaghello, Lizzia
Sambuceti, Gianmario
Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt
title Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt
title_full Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt
title_fullStr Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt
title_full_unstemmed Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt
title_short Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt
title_sort discovery of a novel glucose metabolism in cancer: the role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848551/
https://www.ncbi.nlm.nih.gov/pubmed/27121192
http://dx.doi.org/10.1038/srep25092
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