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- Title
Cancer metabolism meets systems biology: Pyruvate kinase isoform PKM2 is a metabolic master regulator.
- Authors
Filipp, Fabian V.
- Abstract
Pyruvate kinase activity is controlled by a tightly woven regulatory network. The oncofetal isoform of pyruvate kinase (PKM2) is a master regulator of cancer metabolism. PKM2 engages in parallel, feed-forward, positive and negative feedback control contributing to cancer progression. Besides its metabolic role, non-metabolic functions of PKM2 as protein kinase and transcriptional coactivator for c-MYC and hypoxia-inducible factor 1-alpha are essential for epidermal growth factor receptor activation-induced tumorigenesis. These biochemical activities are controlled by a shift in the oligomeric state of PKM2 that includes acetylation, oxidation, phosphorylation, prolyl hydroxylation and sumoylation. Metabolically active PKM2 tetramer is allosterically regulated and responds to nutritional and stress signals. Metabolically inactive PKM2 dimer is imported into the nucleus and can function as protein kinase stimulating transcription. A systems biology approach to PKM2 at the genome, transcriptome, proteome, metabolome and luxome level reveals how differences in biomolecular structure translate into a global rewiring of cancer metabolism. Cancer systems biology takes us beyond the Warburg effect, opening unprecedented therapeutic opportunities.
- Subjects
SYSTEMS biology; CANCER cells; CELL metabolism; PYRUVATE kinase; CANCER invasiveness; GENETIC transcription regulation; HYPOXIA-inducible factor 1
- Publication
Journal of Carcinogenesis, 2012, p1
- ISSN
0974-6773
- Publication type
Article
- DOI
10.4103/1477-3163.115423