Glutamate production from ammonia via glutamate dehydrogenase 2 activity supports cancer cell proliferation under glutamine depletion

• Takeuchi, Yukiko

• Nakayama, Yasumune

• Fukusaki, Eiichiro

• Irino, Yasuhiro

Abstract

Cancer cells rapidly consume glutamine as a carbon and nitrogen source to support proliferation, but the cell number continues to increase exponentially after glutamine is nearly depleted from the medium. In contrast, cell proliferation rates are strongly depressed when cells are cultured in glutamine-free medium. How cancer cells survive in response to nutrient limitation and cellular stress remains poorly understood. In addition, rapid glutamine catabolism yields ammonia, which is a potentially toxic metabolite that is secreted into the extracellular space. Here, we show that ammonia can be utilized for glutamate production, leading to cell proliferation under glutamine-depleted conditions. This proliferation requires glutamate dehydrogenase 2, which synthesizes glutamate from ammonia and cc-ketoglutarate and is expressed in MCF7 and T47D cells. Our findings provide insight into how cancer cells survive under glutamine deprivation conditions and thus contribute to elucidating the mechanisms of tumor growth.

Journal

• Biochemical and Biophysical Research Communications

  Biochemical and Biophysical Research Communications 495 (1), 761-767, 2018-01-01

  Elsevier

Keywords

• Ammonia
• Cancer
• Glutamate
• Glutamate dehydrogenase
• Proliferation

Details

• CRID: 1050012570393360000
• NII Article ID: 120006545118
• DOI: 10.1016/j.bbrc.2017.11.088
• ISSN: 10902104
• ISSN: 0006291X
• HANDLE: 20.500.14094/90005457
• Web Site: https://api.elsevier.com/content/article/PII:S0006291X17322660?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0006291X17322660?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN