Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Edwards-Hicks, J; Su, H; Mangolini, M; Yoneten, KK; Wills, J; Rodriguez-Blanco, G; Young, C; Cho, K; Barker, H; Muir, M; Guerrieri, AN; Li, XF; White, R; Manasterski, P; Mandrou, E; Wills, K; Chen, J; Abraham, E; Sateri, K; Qian, BZ; Bankhead, P; Arends, M; Gammoh, N; von, Kriegsheim, A; Patti, GJ; Sims, AH; Acosta, JC; Brunton, V; Kranc, KR; Christophorou, M; Pearce, EL; Ringshausen, I; Finch, AJ.
MYC sensitises cells to apoptosis by driving energetic demand.
Nat Commun. 2022; 13(1): 4674
Doi: 10.1038/s41467-022-32368-z
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- Rodriguez Blanco Giovanny
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- Abstract:
- The MYC oncogene is a potent driver of growth and proliferation but also sensitises cells to apoptosis, which limits its oncogenic potential. MYC induces several biosynthetic programmes and primary cells overexpressing MYC are highly sensitive to glutamine withdrawal suggesting that MYC-induced sensitisation to apoptosis may be due to imbalance of metabolic/energetic supply and demand. Here we show that MYC elevates global transcription and translation, even in the absence of glutamine, revealing metabolic demand without corresponding supply. Glutamine withdrawal from MRC-5 fibroblasts depletes key tricarboxylic acid (TCA) cycle metabolites and, in combination with MYC activation, leads to AMP accumulation and nucleotide catabolism indicative of energetic stress. Further analyses reveal that glutamine supports viability through TCA cycle energetics rather than asparagine biosynthesis and that TCA cycle inhibition confers tumour suppression on MYC-driven lymphoma in vivo. In summary, glutamine supports the viability of MYC-overexpressing cells through an energetic rather than a biosynthetic mechanism.
- Find related publications in this database (using NLM MeSH Indexing)
- Apoptosis - genetics
- Cell Line, Tumor - administration & dosage
- Citric Acid Cycle - administration & dosage
- Fibroblasts - metabolism
- Glutamine - metabolism
- Proto-Oncogene Proteins c-myc - genetics, metabolism