PKM2 contributes to cancer metabolism

Warburg, 1927, The metabolism of tumors in the body, J. Gen. Physiol., 8, 519, 10.1085/jgp.8.6.519 Warburg, 1956, On the origin of cancer cells, Science, 123, 309, 10.1126/science.123.3191.309 Stryer, 1995 Grüning, 2011, Pyruvate kinase triggers a metabolic feedback loop that controls redox metabolism in respiring cells, Cell Metab., 14, 415, 10.1016/j.cmet.2011.06.017 Noguchi, 1987, The L- and R-type isozymes of rat pyruvate kinase are produced from a single gene by use of different promoters, J. Biol. Chem., 262, 14366, 10.1016/S0021-9258(18)47947-1 Noguchi, 1986, The M1- and M2-type isozymes of rat pyruvate kinase are produced from the same gene by alternative RNA splicing, J. Biol. Chem., 261, 13807, 10.1016/S0021-9258(18)67091-7 Yamada, 1999, Nutrient and hormonal regulation of pyruvate kinase gene expression, Biochem. J., 337, 1, 10.1042/0264-6021:3370001 Imamura, 1972, Multimolecular forms of pyruvate kinase from rat and other mammalian tissues. I. Electrophoretic studies, J. Biochem., 71, 1043, 10.1093/oxfordjournals.jbchem.a129852 Chaneton, 2012, Rocking cell metabolism: revised functions of the key glycolytic regulator PKM2 in cancer, Trends Biochem. Sci., 37, 309, 10.1016/j.tibs.2012.04.003 Muñoz, 2003, Pyruvate kinase: current status of regulatory and functional properties, Comp. Biochem. Physiol. B: Biochem. Mol. Biol., 135, 197, 10.1016/S1096-4959(03)00081-2 Bluemlein, 2011, No evidence for a shift in pyruvate kinase PKM1 to PKM2 expression during tumorigenesis, Oncotarget, 2, 393, 10.18632/oncotarget.278 Desai, 2013, Tissue-specific isoform switch and DNA hypomethylation of the pyruvate kinase PKM gene in human cancers, Oncotarget Mazurek, 2005, Pyruvate kinase type M2 and its role in tumor growth and spreading, Semin. Cancer Biol., 15, 300, 10.1016/j.semcancer.2005.04.009 Saheki, 1978, Hybrid isozymes of rat pyruvate kinase. Their subunit structure and developmental changes in the liver, Biochim. Biophys. Acta, 526, 116, 10.1016/0005-2744(78)90296-6 Mazurek, 2011, Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells, Int. J. Biochem. Cell Biol., 43, 969, 10.1016/j.biocel.2010.02.005 Stuart, 1979, Crystal structure of cat muscle pyruvate kinase at a resolution of 2.6 A, J. Mol. Biol., 134, 109, 10.1016/0022-2836(79)90416-9 Muirhead, 1986, The structure of cat muscle pyruvate kinase, EMBO J., 5, 475, 10.1002/j.1460-2075.1986.tb04236.x Luo, 2011, Pyruvate kinase M2 regulates glucose metabolism by functioning as a coactivator for hypoxia-inducible factor 1 in cancer cells, Oncotarget, 2, 551, 10.18632/oncotarget.299 Morgan, 2013, M2 pyruvate kinase provides a mechanism for nutrient sensing and regulation of cell proliferation, Proc. Natl. Acad. Sci. USA, 110, 5881, 10.1073/pnas.1217157110 Gui, 2013, Allosteric regulation of PKM2 allows cellular adaptation to different physiological states, Sci. Signal., 6, pe7, 10.1126/scisignal.2003925 Luo, 2011, Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1, Cell, 145, 732, 10.1016/j.cell.2011.03.054 Luo, 2012, Emerging roles of PKM2 in cell metabolism and cancer progression, Trends Endocrinol. Metab., 23, 560, 10.1016/j.tem.2012.06.010 David, 2010, HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer, Nature, 463, 364, 10.1038/nature08697 Miller, 2012, c-Myc and cancer metabolism, Clin. Cancer Res., 18, 5546, 10.1158/1078-0432.CCR-12-0977 Garcia-Cao, 2012, Systemic elevation of PTEN induces a tumor-suppressive metabolic state, Cell, 149, 49, 10.1016/j.cell.2012.02.030 Gao, 2012, Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase, Mol. Cell, 45, 598, 10.1016/j.molcel.2012.01.001 Christofk, 2008, The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumor growth, Nature, 452, 230, 10.1038/nature06734 Brinck, 1994, L- and M2-pyruvate kinase expression in renal cell carcinomas and their metastases, Virchows Arch., 424, 177, 10.1007/BF00193498 Schneider, 2002, Tumor M2-pyruvate kinase in lung cancer patients: immunohistochemical detection and disease monitoring, Anticancer Res., 22, 311 Wechsel, 1999, Marker for renal cell carcinoma (RCC): the dimeric form of pyruvate kinase type M2 (Tu M2-PK), Anticancer Res., 19, 2583 Oremek, 1999, The pyruvate kinase isoenzyme tumor M2 (Tu M2-PK) as a tumor marker for renal carcinoma, Anticancer Res., 19, 2599 Pottek, 2000, Tu-M2-PK in the blood of testicular and cubital veins in men with testicular cancer, Anticancer Res., 20, 5029 Eigenbrodt, 1977, Quantification of tumor type M2 pyruvate kinase (Tu M2-PK) in human carcinomas, Anticancer Res., 17, 3153 Lüftner, 2000, Tumor type M2 pyruvate kinase expression in advanced breast cancer, Anticancer Res., 20, 5077 Roigas, 2001, Tumor M2 pyruvate kinase in plasma of patients with urological tumors, Tumour Biol., 22, 282, 10.1159/000050628 Hardt, 2003, Measurement of fecal pyruvate kinase type M2 (tumor M2-PK) concentrations in patients with gastric cancer, colorectal cancer, colorectal adenomas and controls, Anticancer Res., 23, 851 Gordon, 2009, Four-gene expression ratio test for survival in patients undergoing surgery for mesothelioma, J. Natl Cancer Inst., 101, 678, 10.1093/jnci/djp061 Lim, 2012, Overexpression of the M2 isoform of pyruvate kinase is an adverse prognostic factor for signet ring cell gastric cancer, World J. Gastroenterol., 18, 4037, 10.3748/wjg.v18.i30.4037 Zhan, 2013, Pyruvate kinase M2 is highly correlated with the differentiation and the prognosis of esophageal squamous cell cancer, Dis. Esophagus, 26, 746 Feng, 2013, Aberrant overexpression of pyruvate kinase M2 is associated with aggressive tumor features and the BRAF mutation in papillary thyroid cancer, J. Clin. Endocrinol. Metab., 98, E1524, 10.1210/jc.2012-4258 Karachaliou, 2013, Predictive value of BRCA1, ERCC1, ATP7B, PKM2, TOPOI, TOPO-IIA, TOPOIIB and C-MYC genes in patients with small cell lung cancer (SCLC) who received first line therapy with cisplatin and etoposide, PLoS ONE, 8, e74611, 10.1371/journal.pone.0074611 Li, 2013, PKM2 and ACVR 1C are prognostic markers for poor prognosis of gallbladder cancer, Clin. Transl. Oncol. Chiavarina, 2011, Pyruvate kinase expression (PKM1 and PKM2) in cancer-associated fibroblasts drives stromal nutrient production and tumor growth, Cancer Biol. Ther., 12, 1101, 10.4161/cbt.12.12.18703 Imamura, 1982, Pyruvate kinase isozymes from rat, Methods Enzymol., 90, 150, 10.1016/S0076-6879(82)90121-5 van Veelen, 1977, Alanine inhibition of pyruvate kinase in gliomas and meningiomas. A diagnostic tool in surgery for gliomas?, Lancet, 2, 384, 10.1016/S0140-6736(77)90308-7 Vander Heiden, 2010, Identification of small molecule inhibitors of pyruvate kinase M2, Biochem. Pharmacol., 79, 1118, 10.1016/j.bcp.2009.12.003 Anastasiou, 2012, Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis, Nat. Chem. Biol., 8, 839, 10.1038/nchembio.1060 Kung, 2012, Small molecule activation of PKM2 in cancer cells induces serine auxotrophy, Chem. Biol., 19, 1187, 10.1016/j.chembiol.2012.07.021 Parnell, 2013, Pharmacologic activation of PKM2 slows lung tumor xenograft growth, Mol. Cancer Ther., 12, 1453, 10.1158/1535-7163.MCT-13-0026 Dombrauckas, 2005, Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis, Biochemistry, 44, 9417, 10.1021/bi0474923 Ashizawa, 1991, An in vitro novel mechanism of regulating the activity of pyruvate kinase M2 by thyroid hormone and fructose 1,6-bisphosphate, Biochemistry, 30, 7105, 10.1021/bi00243a010 Ashizawa, 1991, In vivo regulation of monomer–tetramer conversion of pyruvate kinase subtype M2 by glucose is mediated via fructose 1,6-bisphosphate, J. Biol. Chem., 266, 16842, 10.1016/S0021-9258(18)55378-3 Presek, 1988, Pyruvate kinase type M2 is phosphorylated at tyrosine residues in cells transformed by Rous sarcoma virus, Fed. Eur. Biochem. Soc. Lett., 242, 194, 10.1016/0014-5793(88)81014-7 Hitosugi, 2009, Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth, Sci. Signal., 2, 97, 10.1126/scisignal.2000431 McDonnell, 2013, Integrated phosphoproteomic and metabolomic profiling reveals NPM-ALK-mediated phosphorylation of PKM2 and metabolic reprogramming in anaplastic large cell lymphoma, Blood, 122, 958, 10.1182/blood-2013-01-482026 Yu, 2013, PIM2 phosphorylates PKM2 and promotes Glycolysis in Cancer Cells, J. Biol. Chem. Bond, 2000, Determinants of allosteric activation of yeast pyruvate kinase and identification of novel effectors using computational screening, Biochemistry, 39, 15333, 10.1021/bi001443i Ikeda, 2000, Dominant negative role of the glutamic acid residue conserved in the pyruvate kinase M(1) isozyme in the heterotropic allosteric effect involving fructose-1,6-bisphosphate, J. Biol. Chem., 275, 9150, 10.1074/jbc.275.13.9150 Lv, 2013, Mitogenic and oncogenic stimulation of K433 acetylation promotes PKM2 protein kinase activity and nuclear localization, Mol. Cell, 52, 340, 10.1016/j.molcel.2013.09.004 Lv, 2011, Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth, Mol. Cell, 42, 719, 10.1016/j.molcel.2011.04.025 Anastasiou, 2011, Cantley, Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses, Science, 334, 1278, 10.1126/science.1211485 Ibsen, 1976, Inhibition of chicken pyruvate kinases by amino acids, Biochemistry, 15, 1073, 10.1021/bi00650a018 Eigenbrodt, 1983, Structural and kinetic differences between the M2 type pyruvate kinases from lung and various tumors, Biomed. Biochim. Acta, 42, S278 Chaneton, 2012, Serine is a natural ligand and allosteric activator of pyruvate kinase M2, Nature, 491, 458, 10.1038/nature11540 Keller, 2012, SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions, Science, 338, 1069, 10.1126/science.1224409 Shimada, 2008, Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein, Genes Cells, 13, 245, 10.1111/j.1365-2443.2008.01165.x Varghese, 2010, Prolactin inhibits activity of pyruvate kinase M2 to stimulate cell proliferation, Mol. Endocrinol., 24, 2356, 10.1210/me.2010-0219 Kosugi, 2011, MUC1-C oncoprotein regulates glycolysis and pyruvate kinase M2 activity in cancer cells, PLoS ONE, 6, e28234, 10.1371/journal.pone.0028234 Mor, 2012, Death-associated protein kinase increases glycolytic rate through binding and activation of pyruvate kinase, Oncogene, 31, 683, 10.1038/onc.2011.264 Christofk, 2008, Pyruvate kinase M2 is a phosphotyrosine-binding protein, Nature, 452, 181, 10.1038/nature06667 Sun, 2011, Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth, Proc. Natl. Acad. Sci. USA, 108, 4129, 10.1073/pnas.1014769108 Iqbal, 2012, Resveratrol inhibits cancer cell metabolism by down regulating pyruvate kinase M2 via inhibition of mammalian target of rapamycin, PLoS ONE, 7, e36764, 10.1371/journal.pone.0036764 Ye, 2012, Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation, Proc. Natl. Acad. Sci. USA, 109, 6904, 10.1073/pnas.1204176109 Gordan, 2007, HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation, Cancer Cell, 12, 108, 10.1016/j.ccr.2007.07.006 Liu, 2012, Targeted genes and interacting proteins of hypoxia inducible factor-1, Int. J. Biochem. Mol. Biol., 3, 165 Wang, 1995, Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension, Proc. Natl. Acad. Sci. USA, 92, 5510, 10.1073/pnas.92.12.5510 Semenza, 1998, Hypoxia-inducible factor 1: master regulator of O2 homeostasis, Curr. Opin. Genet. Dev., 8, 588, 10.1016/S0959-437X(98)80016-6 Jaakkola, 2001, Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation, Science, 292, 468, 10.1126/science.1059796 Ivan, 2001, HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing, Science, 292, 464, 10.1126/science.1059817 Kaelin, 2008, Oxygen sensing by metazoans; the central role of the HIF hydroxylase pathway, Mol. Cell, 30, 393, 10.1016/j.molcel.2008.04.009 Song, 2008, Hypoxia-inducible factor-1alpha-induced differentiation of myeloid leukemic cells is its transcriptional activity independent, Oncogene, 27, 519, 10.1038/sj.onc.1210670 Wenger, 1997, Oxygen(es) and the hypoxia-inducible factor-1, Biol. Chem., 378, 609 Semenza, 2010, HIF-1: upstream and downstream of cancer metabolism, Curr. Opin. Genet. Dev., 20, 51, 10.1016/j.gde.2009.10.009 Meijer, 2012, Targeting hypoxia, HIF-1, and tumor glucose metabolism to improve radiotherapy efficacy, Clin. Cancer Res., 18, 5585, 10.1158/1078-0432.CCR-12-0858 Laughner, 2001, HER2 (neu) signalling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression, Mol. Cell. Biol., 21, 3995, 10.1128/MCB.21.12.3995-4004.2001 Chen, 2012, Turning on a fuel switch of cancer: hnRNP proteins regulate alternative splicing of pyruvate kinase mRNA, Cancer Res., 70, 8977, 10.1158/0008-5472.CAN-10-2513 Tamada, 2012, Pyruvate kinase m2: multiple faces for conferring benefits on cancer cells, Clin. Cancer Res., 18, 5554, 10.1158/1078-0432.CCR-12-0859 Clower, 2010, The alternative splicing repressors of hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism, Proc. Natl. Acad. Sci. USA, 107, 1894, 10.1073/pnas.0914845107 Yang, 2011, Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation, Nature, 480, 118, 10.1038/nature10598 Harris, 2012, PKM2: a gatekeeper between growth and survival, Cell Res., 22, 447, 10.1038/cr.2011.203 Sun, 2012, MiR-124, miR-137 and miR-340 regulate colorectal cancer growth via inhibition of the Warburg effect, Oncol. Rep., 28, 1346, 10.3892/or.2012.1958 Hoshino, 2007, Regulation of cell proliferation by interleukin-3-induced nuclear translocation of pyruvate kinase, J. Biol. Chem., 282, 17706, 10.1074/jbc.M700094200 Steták, 2007, Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death, Cancer Res., 67, 1602, 10.1158/0008-5472.CAN-06-2870 Lee, 2008, Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription, Int. J. Biochem. Cell Biol., 40, 1043, 10.1016/j.biocel.2007.11.009 Wu, 2013, Dual roles of PKM2 in cancer metabolism, Acta Biochim. Biophys. Sin. (Shanghai), 45, 27, 10.1093/abbs/gms106 Spoden, 2009, The SUMO-E3 ligase PIAS3 targets pyruvate kinase M2, J. Cell. Biochem., 107, 293, 10.1002/jcb.22125 Yang, 2012, ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect, Nat. Cell Biol., 14, 1295, 10.1038/ncb2629 Yang, 2012, PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis, Cell, 150, 685, 10.1016/j.cell.2012.07.018 Canal, 2012, PKM2: a new player in the β-catenin game, Future Oncol., 8, 395, 10.2217/fon.12.11 Semenova, 2012, PKM2 enters the morpheein academy, Mol. Cell, 45, 583, 10.1016/j.molcel.2012.02.014 Cortés-Cros, 2013, M2 isoform of pyruvate kinase is dispensable for tumor maintenance and growth, Proc. Natl. Acad. Sci. USA, 110, 489, 10.1073/pnas.1212780110 Israelsen, 2013, PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells, Cell, 155, 397, 10.1016/j.cell.2013.09.025