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Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation

Non-small-cell lung cancer (NSCLC) cell lines vary in their sensitivity to glutaminase inhibitors, so it is important to identify the metabolic assets underling their efficacy in cancer cells. Even though specific genetic lesions such as in KRAS and LKB1 have been associated with reliance on glutami...

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Autores principales: Caiola, Elisa, Colombo, Marika, Sestito, Giovanna, Lupi, Monica, Marabese, Mirko, Pastorelli, Roberta, Broggini, Massimo, Brunelli, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465377/
https://www.ncbi.nlm.nih.gov/pubmed/32718002
http://dx.doi.org/10.3390/cells9081766
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author Caiola, Elisa
Colombo, Marika
Sestito, Giovanna
Lupi, Monica
Marabese, Mirko
Pastorelli, Roberta
Broggini, Massimo
Brunelli, Laura
author_facet Caiola, Elisa
Colombo, Marika
Sestito, Giovanna
Lupi, Monica
Marabese, Mirko
Pastorelli, Roberta
Broggini, Massimo
Brunelli, Laura
author_sort Caiola, Elisa
collection PubMed
description Non-small-cell lung cancer (NSCLC) cell lines vary in their sensitivity to glutaminase inhibitors, so it is important to identify the metabolic assets underling their efficacy in cancer cells. Even though specific genetic lesions such as in KRAS and LKB1 have been associated with reliance on glutamine for their metabolic needs, we found no distinction between glutaminase inhibitor CB-839 sensitivity and resistant phenotypes in NSCLC cells with or without these genetic alterations. We demonstrated the close relationship between environmental alanine uptake and catabolism. This response depended on the individual cell’s ability to employ alanine aminotransferase (GPT2) to compensate the reduced glutamate availability. It may, therefore, be useful to determine GPT2 levels to predict which NSCLC patients would benefit most from glutaminase inhibitor treatment.
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spelling pubmed-74653772020-09-04 Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation Caiola, Elisa Colombo, Marika Sestito, Giovanna Lupi, Monica Marabese, Mirko Pastorelli, Roberta Broggini, Massimo Brunelli, Laura Cells Article Non-small-cell lung cancer (NSCLC) cell lines vary in their sensitivity to glutaminase inhibitors, so it is important to identify the metabolic assets underling their efficacy in cancer cells. Even though specific genetic lesions such as in KRAS and LKB1 have been associated with reliance on glutamine for their metabolic needs, we found no distinction between glutaminase inhibitor CB-839 sensitivity and resistant phenotypes in NSCLC cells with or without these genetic alterations. We demonstrated the close relationship between environmental alanine uptake and catabolism. This response depended on the individual cell’s ability to employ alanine aminotransferase (GPT2) to compensate the reduced glutamate availability. It may, therefore, be useful to determine GPT2 levels to predict which NSCLC patients would benefit most from glutaminase inhibitor treatment. MDPI 2020-07-23 /pmc/articles/PMC7465377/ /pubmed/32718002 http://dx.doi.org/10.3390/cells9081766 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Caiola, Elisa
Colombo, Marika
Sestito, Giovanna
Lupi, Monica
Marabese, Mirko
Pastorelli, Roberta
Broggini, Massimo
Brunelli, Laura
Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation
title Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation
title_full Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation
title_fullStr Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation
title_full_unstemmed Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation
title_short Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation
title_sort glutaminase inhibition on nsclc depends on extracellular alanine exploitation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465377/
https://www.ncbi.nlm.nih.gov/pubmed/32718002
http://dx.doi.org/10.3390/cells9081766
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