{"title":"Cancer metabolism meets systems biology: Pyruvate kinase isoform PKM2 is a metabolic master regulator.","authors":"Fabian V Filipp","doi":"10.4103/1477-3163.115423","DOIUrl":null,"url":null,"abstract":"<p><p>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 fluxome 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. </p>","PeriodicalId":52464,"journal":{"name":"Journal of Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2013-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/1477-3163.115423","citationCount":"50","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Carcinogenesis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4103/1477-3163.115423","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2013/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"Environmental Science","Score":null,"Total":0}
引用次数: 50
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 fluxome 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.
期刊介绍：
Journal of Carcinogenesis considers manuscripts in many areas of carcinogenesis and Chemoprevention. Primary areas of interest to the journal include: physical and chemical carcinogenesis and mutagenesis; processes influencing or modulating carcinogenesis, such as DNA repair; genetics, nutrition, and metabolism of carcinogens; the mechanism of action of carcinogens and modulating agents; epidemiological studies; and, the formation, detection, identification, and quantification of environmental carcinogens. Manuscripts that contribute to the understanding of cancer prevention are especially encouraged for submission
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