丙酮酸激酶M2的新作用：破解瓦伯格效应
New roles for pyruvate kinase M2: working out the Warburg effect.
作者信息
Ferguson Emily C, Rathmell Jeffrey C
机构信息
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
出版信息
Trends Biochem Sci. 2008 Aug;33(8):359-62. doi: 10.1016/j.tibs.2008.05.006. Epub 2008 Jul 4.
Abstract
The origins and role of the Warburg effect have remained uncertain for many years. Two recent studies demonstrate that an embryonic- and cancer-cell-specific isoform of the enzyme pyruvate kinase M2 (PKM2) is regulated by binding to phospho-tyrosine motifs and promotes increased cell growth and tumor development. PKM2 enhances the use of glycolytic intermediates for macromolecular biosynthesis and tumor growth. These findings illustrate the distinct advantages of this metabolic phenotype in cancer cell growth.
摘要
多年来，瓦伯格效应的起源和作用一直不明确。最近的两项研究表明，丙酮酸激酶M2（PKM2）的一种胚胎细胞和癌细胞特异性同工型受磷酸化酪氨酸基序结合调控，并促进细胞生长增加和肿瘤发展。PKM2增强了糖酵解中间产物用于大分子生物合成和肿瘤生长的过程。这些发现说明了这种代谢表型在癌细胞生长中的独特优势。
相似文献
1
New roles for pyruvate kinase M2: working out the Warburg effect.
Trends Biochem Sci. 2008 Aug;33(8):359-62. doi: 10.1016/j.tibs.2008.05.006. Epub 2008 Jul 4.
2
Pyruvate kinase M2: multiple faces for conferring benefits on cancer cells.
Clin Cancer Res. 2012 Oct 15;18(20):5554-61. doi: 10.1158/1078-0432.CCR-12-0859.
3
Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth.
Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4129-34. doi: 10.1073/pnas.1014769108. Epub 2011 Feb 15.
4
Aurora A-mediated pyruvate kinase M2 phosphorylation promotes biosynthesis with glycolytic metabolites and tumor cell cycle progression.
J Biol Chem. 2022 Nov;298(11):102561. doi: 10.1016/j.jbc.2022.102561. Epub 2022 Oct 2.
5
Pyruvate kinase M2 affects liver cancer cell behavior through up-regulation of HIF-1α and Bcl-xL in culture.
Biomed Pharmacother. 2015 Feb;69:277-84. doi: 10.1016/j.biopha.2014.12.010. Epub 2014 Dec 19.
6
Tyrosine Kinase Signaling in Cancer Metabolism: PKM2 Paradox in the Warburg Effect.
Front Cell Dev Biol. 2018 Jul 24;6:79. doi: 10.3389/fcell.2018.00079. eCollection 2018.
7
Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis.
Nat Chem Biol. 2012 Oct;8(10):839-47. doi: 10.1038/nchembio.1060.
8
Insulin enhances metabolic capacities of cancer cells by dual regulation of glycolytic enzyme pyruvate kinase M2.
Mol Cancer. 2013 Jul 9;12:72. doi: 10.1186/1476-4598-12-72.
9
Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions.
World J Gastroenterol. 2019 Apr 28;25(16):1936-1949. doi: 10.3748/wjg.v25.i16.1936.
10
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth.
Nature. 2008 Mar 13;452(7184):230-3. doi: 10.1038/nature06734.
引用本文的文献
1
Metformin Increases the Response of Cholangiocarcinoma Cells to Gemcitabine by Suppressing Pyruvate Kinase M2 to Activate Mitochondrial Apoptosis.
Dig Dis Sci. 2024 Feb;69(2):476-490. doi: 10.1007/s10620-023-08210-x. Epub 2024 Jan 3.
2
Aerobic Glycolysis in Photoreceptors Supports Energy Demand in the Absence of Mitochondrial Coupling.
Adv Exp Med Biol. 2023;1415:435-441. doi: 10.1007/978-3-031-27681-1_64.
3
AFB1 and OTA Promote Immune Toxicity in Human LymphoBlastic T Cells at Transcriptomic Level.
Foods. 2023 Jan 6;12(2):259. doi: 10.3390/foods12020259.
4
Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance.
Int J Mol Sci. 2021 Aug 15;22(16):8754. doi: 10.3390/ijms22168754.
5
Dysfunction of chaperone-mediated autophagy in human diseases.
Mol Cell Biochem. 2021 Mar;476(3):1439-1454. doi: 10.1007/s11010-020-04006-z. Epub 2021 Jan 3.
6
Pyruvate Kinase M2 Coordinates Metabolism Switch between Glycolysis and Glutaminolysis in Cancer Cells.
iScience. 2020 Oct 15;23(11):101684. doi: 10.1016/j.isci.2020.101684. eCollection 2020 Nov 20.
7
Chaperone-Mediated Autophagy and Its Emerging Role in Hematological Malignancies.
Cells. 2019 Oct 16;8(10):1260. doi: 10.3390/cells8101260.
8
Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions.
World J Gastroenterol. 2019 Apr 28;25(16):1936-1949. doi: 10.3748/wjg.v25.i16.1936.
9
Oncogenic Metabolism Acts as a Prerequisite Step for Induction of Cancer Metastasis and Cancer Stem Cell Phenotype.
Oxid Med Cell Longev. 2018 Dec 23;2018:1027453. doi: 10.1155/2018/1027453. eCollection 2018.
10
HSP90 promotes cell glycolysis, proliferation and inhibits apoptosis by regulating PKM2 abundance via Thr-328 phosphorylation in hepatocellular carcinoma.
Mol Cancer. 2017 Dec 20;16(1):178. doi: 10.1186/s12943-017-0748-y.
本文引用的文献
1
Brick by brick: metabolism and tumor cell growth.
Curr Opin Genet Dev. 2008 Feb;18(1):54-61. doi: 10.1016/j.gde.2008.02.003. Epub 2008 Apr 2.
2
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth.
Nature. 2008 Mar 13;452(7184):230-3. doi: 10.1038/nature06734.
3
Pyruvate kinase M2 is a phosphotyrosine-binding protein.
Nature. 2008 Mar 13;452(7184):181-6. doi: 10.1038/nature06667.
4
The biology of cancer: metabolic reprogramming fuels cell growth and proliferation.
Cell Metab. 2008 Jan;7(1):11-20. doi: 10.1016/j.cmet.2007.10.002.
5
Glycogen synthase kinase 3alpha and 3beta mediate a glucose-sensitive antiapoptotic signaling pathway to stabilize Mcl-1.
Mol Cell Biol. 2007 Jun;27(12):4328-39. doi: 10.1128/MCB.00153-07. Epub 2007 Mar 19.
6
Energy metabolism in tumor cells.
FEBS J. 2007 Mar;274(6):1393-418. doi: 10.1111/j.1742-4658.2007.05686.x.
7
Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking.
Mol Biol Cell. 2007 Apr;18(4):1437-46. doi: 10.1091/mbc.e06-07-0593. Epub 2007 Feb 14.
8
Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis.
Biochemistry. 2005 Jul 12;44(27):9417-29. doi: 10.1021/bi0474923.
9
Hypoxia-inducible factor-1alpha and the glycolytic phenotype in tumors.
Neoplasia. 2005 Apr;7(4):324-30. doi: 10.1593/neo.04430.
10
Pyruvate kinase type M2 and its role in tumor growth and spreading.
Semin Cancer Biol. 2005 Aug;15(4):300-8. doi: 10.1016/j.semcancer.2005.04.009.
Zotero 插件