Cell reports · 2019
Uncovering the Role of N-Acetyl-Aspartyl-Glutamate as a Glutamate Reservoir in Cancer.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Nguyen Tu, Kirsch Brian James, Asaka Ryoichi, Nabi Karim, Quinones Addison, Tan Jessica, Antonio Marjorie Justine, Camelo Felipe, Li Ting, Nguyen Stephanie, Hoang Giang, Nguyen Kiet, Udupa Sunag, Sazeides Christos, Shen Yao-An, Elgogary Amira, Reyes Juvenal, Zhao Liang, Kleensang Andre, Chaichana Kaisorn Lee, Hartung Thomas, Betenbaugh Michael J, Marie Suely K, Jung Jin G, Wang Tian-Li, Gabrielson Edward, Le Anne
Аннотация
N-acetyl-aspartyl-glutamate (NAAG) is a peptide-based neurotransmitter that has been extensively studied in many neurological diseases. In this study, we show a specific role of NAAG in cancer. We found that NAAG is more abundant in higher grade cancers and is a source of glutamate in cancers expressing glutamate carboxypeptidase II (GCPII), the enzyme that hydrolyzes NAAG to glutamate and N-acetyl-aspartate (NAA). Knocking down GCPII expression through genetic alteration or pharmacological inhibition of GCPII results in a reduction of both glutamate concentrations and cancer growth. Moreover, targeting GCPII in combination with glutaminase inhibition accentuates these effects. These findings suggest that NAAG serves as an important reservoir to provide glutamate to cancer cells through GCPII when glutamate production from other sources is limited. Thus, GCPII is a viable target for cancer therapy, either alone or in combination with glutaminase inhibition.