Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation

被引：21

作者：

Caiola, Elisa ^{[1
]}

Colombo, Marika ^{[1
]}

Sestito, Giovanna ^{[2
]}

Lupi, Monica ^{[3
]}

Marabese, Mirko ^{[1
]}

Pastorelli, Roberta ^{[2
]}

Broggini, Massimo ^{[1
]}

Brunelli, Laura ^{[2
]}

机构：

[1] Ist Ric Farmacol Mario Negri IRCCS, Lab Mol Pharmacol, Dept Oncol, I-20156 Milan, Italy

[2] Ist Ric Farmacol Mario Negri IRCCS, Lab Mass Spectrometry, Dept Environm Hlth Sci, I-20156 Milan, Italy

[3] Ist Ric Farmacol Mario Negri IRCCS, Lab Antitumor Pharmacol, Dept Oncol, I-20156 Milan, Italy

来源：

CELLS | 2020年 / 9卷 / 08期

关键词：

NSCLC; glutaminase inhibition; metabolism; alanine uptake; cancer cell resistance; alanine aminotransferase; LUNG-CANCER; PYRUVATE-CARBOXYLASE; METABOLISM; CELLS;

D O I：

10.3390/cells9081766

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：12

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