The glutamine-aspartate metabolic tradeoff between fast growth and metabolic flexibility.
Ortmayr, K.; Ringwald, M.; Schuhknecht, L.; Dubuis, S.; Paunossis, E.; Blasi, M.; Jehanno, C.; Grieder, S.; Bentires-Alj, M.; Mall, M.; Zampieri, M.
Show abstract
Cancer cells develop unique addictions to nutrients, offering attractive opportunities for clinical intervention. However, how cancer cells orchestrate and benefit from metabolic rewiring remain fundamental open questions. Here, we developed a systematic framework to investigate nutrient dependencies and applied it to study glutamine addiction. By measuring metabolite exchange rates across 54 cancer cell lines with different levels of dependency on extracellular glutamine and in human stem cells, we discovered that a dualistic regulation of glutamate biosynthesis from glutamine or aspartate, driven by the tissue of origin, generates a tradeoff between fast growth and metabolic flexibility. Monitoring dynamic metabolic adaptation to glutamine deprivation showed that the role of glutamine as limiting substrate in purine biosynthesis is not responsible for glutamine dependency. Rather, growth arrest is mediated by glutamine as a signaling molecule. Our approach opens new opportunities to map, mechanistically investigate and pharmacologically interfere with metabolic dependencies, beyond glutamine addiction.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Multiplex genome editing eliminates the Warburg Effect without impacting growth rate in mammalian cells 95%
- Hexokinase detachment from mitochondria drives the Warburg effect to support compartmentalized ATP production 94%
- Nitrogen metabolism profiling reveals cell state-specific pyrimidine synthesis pathway choice 93%
Similar papers in this journal
- Multilevel Plasticity and Altered Glycosylation Drive Aggressiveness in Hypoxic and Glucose-Deprived Bladder Cancer Cells 94%
- Comparing the impact of sample multiplexing approaches for single-cell RNA-sequencing on downstream analysis using cerebellar organoids 93%
- Metabolic predictors of response to immune checkpoint blockade therapy 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.