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Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation

Published:23 July 2020 DOI: 10.3390/cells9081766 PMID: 32718002
Elisa Caiola, Marika Colombo, Giovanna Sestito, Monica Lupi, Mirko Marabese, Roberta Pastorelli, Massimo Broggini, Laura Brunelli

Abstract

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.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
CB-839 1439399-58-2 C26H24F3N7O3S 157 suppliers $17.00-$2175.00
CB-839 1439399-58-2 C26H24F3N7O3S 157 suppliers $17.00-$2175.00
CB-839 1439399-58-2 C26H24F3N7O3S 157 suppliers $17.00-$2175.00
CB-839 1439399-58-2 C26H24F3N7O3S 157 suppliers $17.00-$2175.00

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