دورية أكاديمية
Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma.
| العنوان: | Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma. |
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| المؤلفون: | Tardito, Saverio, Oudin, Anaïs, Ahmed, Shafiq U, Fack, Fred, Keunen, Olivier, Zheng, Liang, Miletic, Hrvoje, Sakariassen, Per Øystein, Weinstock, Adam, Wagner, Allon, Lindsay, Susan L, Hock, Andreas K, Barnett, Susan C, Ruppin, Eytan, Mørkve, Svein Harald, Lund-Johansen, Morten, Chalmers, Anthony J, Bjerkvig, Rolf, NICLOU, Simone P., Gottlieb, Eyal |
| المصدر: | Nature Cell Biology, 17 (12), 1556 - 1568 (2015-12) |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2015 |
| المجموعة: | University of Luxembourg: ORBilu - Open Repository and Bibliography |
| مصطلحات موضوعية: | Nucleotides, Glutamine, Glutamic Acid, Glutamate-Ammonia Ligase, Animals, Astrocytes/cytology, Astrocytes/metabolism, Blotting, Western, Brain Neoplasms/genetics, Brain Neoplasms/metabolism, Brain Neoplasms/pathology, Cell Line, Tumor, Cells, Cultured, Citric Acid Cycle, Coculture Techniques, Female, Glioblastoma/genetics, Glioblastoma/metabolism, Glioblastoma/pathology, Glutamate-Ammonia Ligase/genetics, Glutamate-Ammonia Ligase/metabolism, Glutamic Acid/metabolism, Glutamine/metabolism, Humans, Male, Mice, Inbred NOD |
| الوصف: | peer reviewed ; L-Glutamine (Gln) functions physiologically to balance the carbon and nitrogen requirements of tissues. It has been proposed that in cancer cells undergoing aerobic glycolysis, accelerated anabolism is sustained by Gln-derived carbons, which replenish the tricarboxylic acid (TCA) cycle (anaplerosis). However, it is shown here that in glioblastoma (GBM) cells, almost half of the Gln-derived glutamate (Glu) is secreted and does not enter the TCA cycle, and that inhibiting glutaminolysis does not affect cell proliferation. Moreover, Gln-starved cells are not rescued by TCA cycle replenishment. Instead, the conversion of Glu to Gln by glutamine synthetase (GS; cataplerosis) confers Gln prototrophy, and fuels de novo purine biosynthesis. In both orthotopic GBM models and in patients, (13)C-glucose tracing showed that GS produces Gln from TCA-cycle-derived carbons. Finally, the Gln required for the growth of GBM tumours is contributed only marginally by the circulation, and is mainly either autonomously synthesized by GS-positive glioma cells, or supplied by astrocytes. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1465-7392 1476-4679 |
| العلاقة: | http://www.nature.com/articles/ncb3272.pdfTest; urn:issn:1465-7392; urn:issn:1476-4679; https://orbilu.uni.lu/handle/10993/60197Test; info:hdl:10993/60197; scopus-id:2-s2.0-84948701108; info:pmid:26595383; wos:000365932300008 |
| DOI: | 10.1038/ncb3272 |
| الإتاحة: | https://doi.org/10.1038/ncb3272Test https://orbilu.uni.lu/handle/10993/60197Test |
| رقم الانضمام: | edsbas.9067D728 |
| قاعدة البيانات: | BASE |
| تدمد: | 14657392 14764679 |
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| DOI: | 10.1038/ncb3272 |