文章基本信息

标题：Pyruvate Kinase M2 Coordinates Metabolism Switch between Glycolysis and Glutaminolysis in Cancer Cells
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作者：Liangwei Li ; Guangda Peng ; Xiaowei Liu 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：11
页码：1-22
DOI：10.1016/j.isci.2020.101684
语种：English
出版社：Elsevier
摘要：SummaryCancer cells alter their nutrition metabolism to cope the stressful environment. One important metabolism adjustment is that cancer cells activate glutaminolysis in response to the reduced carbon from glucose entering into the TCA cycle due to inactivation of several enzymes in glycolysis. An important question is how the cancer cells coordinate the changes of glycolysis and glutaminolysis. In this report, we demonstrate that the pyruvate kinase inactive dimer PKM2 facilitates activation of glutaminolysis. Our experiments show that growth stimulations promote PKM2 dimer. The dimer PKM2 plays a role in regulation of glutaminolysis by upregulation of mitochondrial glutaminase I (GLS-1). PKM2 dimer regulates the GLS-1 expression by controlling internal ribosome entry site (IRES)-dependent c-myc translation. Growth stimulations promote PKM2 interacting with c-myc IRES-RNA, thus facilitating c-myc IRES-dependent translation. Our study reveals an important linker that coordinates the metabolism adjustment in cancer cells.Graphical AbstractDisplay OmittedHighlights•PKM2 coordinates cancer cell glucose and glutamine metabolism under growth stimulations•PKM2 controls cancer cell metabolism by regulating GLS and c-myc expression•PKM2 regulates c-Myc IRES-dependent translation•PKM2 dimer facilitates assembly of hnRNP K/L into c-Myc IRES complexBiological Sciences; Cell Biology; Cancer