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Article

Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation

1
Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy
2
Laboratory of Mass Spectrometry, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy
3
Laboratory of Antitumor Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy
*
Authors to whom correspondence should be addressed.
These authors share co-first authorship.
These authors share co-last authorship.
Cells 2020, 9(8), 1766; https://doi.org/10.3390/cells9081766
Received: 17 February 2020 / Revised: 15 July 2020 / Accepted: 18 July 2020 / Published: 23 July 2020
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. View Full-Text
Keywords: NSCLC; glutaminase inhibition; metabolism; alanine uptake; cancer cell resistance; alanine aminotransferase NSCLC; glutaminase inhibition; metabolism; alanine uptake; cancer cell resistance; alanine aminotransferase
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MDPI and ACS Style

Caiola, E.; Colombo, M.; Sestito, G.; Lupi, M.; Marabese, M.; Pastorelli, R.; Broggini, M.; Brunelli, L. Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation. Cells 2020, 9, 1766. https://doi.org/10.3390/cells9081766

AMA Style

Caiola E, Colombo M, Sestito G, Lupi M, Marabese M, Pastorelli R, Broggini M, Brunelli L. Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation. Cells. 2020; 9(8):1766. https://doi.org/10.3390/cells9081766

Chicago/Turabian Style

Caiola, Elisa, Marika Colombo, Giovanna Sestito, Monica Lupi, Mirko Marabese, Roberta Pastorelli, Massimo Broggini, and Laura Brunelli. 2020. "Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation" Cells 9, no. 8: 1766. https://doi.org/10.3390/cells9081766

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