Abstract IA06: De novo purine biosynthesis dictates glutamine dependency of glioblastoma cells

L-Glutamine has the unique physiological function of balancing carbon and nitrogen requirements of tissues. It has been proposed that cancer cells undergoing aerobic glycolysis require glutamine carbons to replenish the tricarboxylic acid (TCA) cycle and sustain accelerated anabolism (anaplerosis). Yet we showed that, in glioblastoma (GBM) cells, about half of the glutamine-derived glutamate is secreted out of the cells and does not enter the TCA cycle. In the absence of glutamine, replenishment of the TCA cycle is insufficient to restore cell proliferation. In contrast, cataplerotic reactions culminating with the conversion of glutamate to glutamine by Glutamine Synthetase (GS) are sufficient to sustain growth in the absence of glutamine. GS is expressed in ~80% of human GBM tumours, and 13C-glucose tracing showed that GS utilizes TCA cycle-derived carbons to produce glutamine in patients. GS-derived glutamine provides the amide nitrogen for de novo biosynthesis of nucleotides and thereby dictates GBM dependency on glutamine.Citation Format: Eyal Gottlieb. De novo purine biosynthesis dictates glutamine dependency of glioblastoma cells. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr IA06.

Source: Molecular Cancer Research - January 15, 2016 Category: Cancer & Oncology Authors: Gottlieb, E. Tags: Therapeutic Targets From Cancer: Oral Presentations - Invited Abstracts Source Type: research