Pyruvate kinase type M2: A key regulator of the metabolic budget system in tumor cells
Abstract
Cell proliferation only proceeds when metabolism is capable of providing a budget of metabolic intermediates that is adequate to ensure both energy regeneration and the synthesis of cell building blocks in sufficient amounts. In tumor cells, the glycolytic pyruvate kinase isoenzyme M2 (PKM2, M2-PK) determines whether glucose is converted to lactate for regeneration of energy (active tetrameric form, Warburg effect) or used for the synthesis of cell building blocks (nearly inactive dimeric form). This review discusses the regulation mechanisms of pyruvate kinase M2 expression by different transcription factors as well as the regulation of pyruvate kinase M2 activity by direct interaction with certain oncoproteins, tyrosine and serine phosphorylation, binding of phosphotyrosine peptides, association with other glycolytic and non glycolytic enzymes, the promyelocytic leukemia tumor suppressor protein, as well as metabolic intermediates. An intervention in the regulation mechanisms of the expression, activity and tetramer to dimer ratio of pyruvate kinase M2 has severe consequences for metabolism as well as proliferation and tumorigenic capacity of the cells which makes this enzyme a promising target for potential therapeutic approaches. The quantification of the dimeric form of pyruvate kinase M2 (Tumor M2-PK) in plasma and stool allows early detection of tumors and therapy control. Several different mechanisms may induce a translocation of pyruvate kinase M2 into the nucleus. The role of pyruvate kinase M2 in the nucleus is complex as witnessed by evidence of its effect both as pro-proliferative as well as pro-apoptotic stimuli.
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PKM2 splice variant is expressed in embryonic tissues, proliferating cells, and tumor cells.
“The muscle version of PK exists as one of two isoforms, M1 or M2, generated from differential splicing of the PKM primary mRNA transcript, with the PKM2 splice variant expressed in embryonic tissues, proliferating cells, and tumor cells (54).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [54]
Cites
Why Do Cancers Have High Aerobic Glycolysis?
Gatenby, R. A., & Gillies, R. J. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1478 · Cited by 4,784 · see citing works
Papillomaviruses and cancer: from basic studies to clinical application
Hausen, H. Z. (2002) · Nature reviews. Cancer · doi:10.1038/nrc798 · Cited by 4,031 · see citing works
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
Christofk, H. R., Vander Heiden, M. G., Harris, M. H., Ramanathan, A., Gerszten, R. E., Wei, R., Fleming, M. D., Schreiber, S. L., & Cantley, L. C. (2008) · Nature · doi:10.1038/nature06734 · Cited by 2,820 · see citing works
DeBerardinis, R. J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S., & Thompson, C. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709747104 · Cited by 2,622 · see citing works
Fantin, V. R., St-Pierre, J., & Leder, P. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.04.023 · Cited by 1,635 · see citing works
Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells.
Reitzer, L. J., Wice, B. M., & Kennell, D. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)30124-2 · Cited by 1,240 · see citing works
HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer
David, C. J., Chen, M., Assanah, M., Canoll, P., & Manley, J. L. (2010) · Nature · doi:10.1038/nature08697 · Cited by 1,179 · see citing works
Marshall, S., Bacote, V., & Traxinger, R. R. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)67706-9 · Cited by 1,049 · see citing works
Pyruvate kinase M2 is a phosphotyrosine-binding protein
Christofk, H. R., Vander Heiden, M. G., Wu, N., Asara, J. M., & Cantley, L. C. (2008) · Nature · doi:10.1038/nature06667 · Cited by 995 · see citing works
Energy Substrate Modulates Mitochondrial Structure and Oxidative Capacity in Cancer Cells
Rossignol, R., Gilkerson, R., Aggeler, R., Yamagata, K., Remington, S., & Capaldi, R. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-1101 · Cited by 865 · see citing works
Pyruvate kinase type M2 and its role in tumor growth and spreading
Mazurek, S., Boschek, C. B., Hugo, F., & Eigenbrodt, E. (2005) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2005.04.009 · Cited by 812 · see citing works
Self-citationTyrosine Phosphorylation Inhibits PKM2 to Promote the Warburg Effect and Tumor Growth
Hitosugi, T., Kang, S., Vander Heiden, M. G., Chung, T.-W., Elf, S., Lythgoe, K., Dong, S., Lonial, S., Wang, X., Chen, G. Z., et al. (2009) · Science Signaling · doi:10.1126/scisignal.2000431 · Cited by 784 · see citing works
Tumor-derived lactic acid modulates dendritic cell activation and antigen expression
Gottfried, E., Kunz-Schughart, L. A., Ebner, S., Mueller-Klieser, W., Hoves, S., Andreesen, R., Mackensen, A., & Kreutz, M. (2006) · Blood · doi:10.1182/blood-2005-05-1795 · Cited by 729 · see citing works
Noguchi, T., Inoue, H., & Tanaka, T. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)67091-7 · Cited by 544 · see citing works
Role of PML in Cell Growth and the Retinoic Acid Pathway
Wang, Z. G., Delva, L., Gaboli, M. P., Rivi, R., Giorgio, M., Cordon‐Cardo, C., Grosveld, F. G., & Pandolfi, P. P. (1998) · Science · doi:10.1126/science.279.5356.1547 · Cited by 516 · see citing works
MEMBRANE-ASSOCIATED GUANYLATE KINASES REGULATE ADHESION AND PLASTICITY AT CELL JUNCTIONS
Funke, L., Dakoji, S., & Bredt, D. S. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133339 · Cited by 469 · see citing works
The bioenergetic signature of cancer: a marker of tumor progression.
Cuezva, J. M., Krajewska, M., de Heredia, M. L., Krajewski, S., Santamaría, G., Kim, H., Zapata, J. M., Marusawa, H., Chamorro, M., & Reed, J. C. (2002) · PubMed · Cited by 440 · see citing works
Lactate: mirror and motor of tumor malignancy
Walenta, S., & Mueller‐Klieser, W. (2004) · Seminars in Radiation Oncology · doi:10.1016/j.semradonc.2004.04.004 · Cited by 432 · see citing works
Structural Basis for Tumor Pyruvate Kinase M2 Allosteric Regulation and Catalysis ,
Dombrauckas, J. D., Santarsiero, B. D., & Mesecar, A. D. (2005) · Biochemistry · doi:10.1021/bi0474923 · Cited by 414 · see citing works
Kim, J.-W., Zeller, K. I., Wang, Y., Jegga, A. G., Aronow, B. J., O'Donnell, K. A., & Dang, C. V. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.13.5923-5936.2004 · Cited by 371 · see citing works
Nagy, E., & Rigby, W. F. C. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.6.2755 · Cited by 361 · see citing works
Noguchi, T., Yamada, K., Inoue, H., Matsuda, T., & Tanaka, T. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47947-1 · Cited by 332 · see citing works
Pyrimidine pathways in health and disease
Löffler, M., Fairbanks, L. D., Zameitat, E., Marinaki, A. M., & Simmonds, H. A. (2005) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2005.07.003 · Cited by 278 · see citing works
Modulation of type M 2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein
Zwerschke, W., Mazurek, S., Massimi, P., Banks, L., EIGENBRODT, E., & Jansen‐Dürr, P. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.4.1291 · Cited by 257 · see citing works
Self-citationMetabolic analysis of senescent human fibroblasts reveals a role for AMP in cellular senescence
Zwerschke, W., Mazurek, S., Stöckl, P., Hütter, E., EIGENBRODT, E., & Jansen‐Dürr, P. (2003) · Biochemical Journal · doi:10.1042/bj20030816 · Cited by 248 · see citing works
Self-citationIdentification of small molecule inhibitors of pyruvate kinase M2
Heiden, M. G. V., Christofk, H. R., Schuman, E., Subtelny, A. O., Sharfi, H., Harlow, E. E., Xian, J., & Cantley, L. C. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.12.003 · Cited by 239 · see citing works
Makino, S., van Putten, J. P. M., & Meyer, T. F. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb07649.x · Cited by 226 · see citing works
Three glycolytic enzymes are phosphorylated at tyrosine in cells transformed by Rous sarcoma virus
Cooper, J. A., Reiss, N. A., Schwartz, R. J., & Hunter, T. R. (1983) · Nature · doi:10.1038/302218a0 · Cited by 222 · see citing works
Renner, E. D., Plagemann, P. G. W., & Bernlohr, R. W. (1972) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)44825-4 · Cited by 217 · see citing works
Lee, J., Kim, H., Han, Y., & Kim, J. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.11.009 · Cited by 214 · see citing works
EIGENBRODT, E., Reinacher, M., Scheefers-Borchel, U., SCHEEFERS, H., & Friis, R. R. (1992) · PubMed · Cited by 210 · see citing works
Wong, T., Liu, X., Ho, A. C., Yuen, A. P. W., Ng, R. W. M., & Wei, W. (2008) · International Journal of Cancer · doi:10.1002/ijc.23583 · Cited by 188 · see citing works
Nutrient and hormonal regulation of pyruvate kinase gene expression
Yamada, K., & Noguchi, T. (1998) · Biochemical Journal · doi:10.1042/bj3370001 · Cited by 185 · see citing works
Nuclear Translocation of the Tumor Marker Pyruvate Kinase M2 Induces Programmed Cell Death
Steták, A., Veress, R., Ovádi, J., Csermely, P., Kéri, G., & Ullrich, A. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2870 · Cited by 183 · see citing works
Ashizawa, K., Willingham, M. C., Liang, C. M., & Cheng, S. Y. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)55378-3 · Cited by 172 · see citing works
Discher, D. J., Bishopric, N. H., Wu, X., Peterson, C. A., & Webster, K. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.40.26087 · Cited by 166 · see citing works
Pyruvate kinase type M2: a crossroad in the tumor metabolome
Mazurek, S., Grimm, H., Boschek, C. B., Vaupel, P. W., & EIGENBRODT, E. (2002) · British Journal Of Nutrition · doi:10.1079/bjn2001454 · Cited by 159 · see citing works
Self-citationDing, S., Li, Y., Shao, X., Zhou, H., Zeng, R., Tang, Z., & Xia, Q. (2004) · PROTEOMICS · doi:10.1002/pmic.200300653 · Cited by 154 · see citing works
Mitochondria: from bioenergetics to the metabolic regulation of carcinogenesis
Bellancé, N. (2009) · Frontiers in bioscience · doi:10.2741/3509 · Cited by 153 · see citing works
LOBO, C., RUIZ-BELLIDO, M. A., ALEDO, J. C., MÁRQUEZ, J., NÚÑEZ DE CASTRO, I., & ALONSO, F. J. (2000) · Biochemical Journal · doi:10.1042/bj3480257 · Cited by 151 · see citing works
Mazurek, S., Zwerschke, W., Jansen‐Dürr, P., & EIGENBRODT, E. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3560247 · Cited by 147 · see citing works
Self-citationMultisite control of the Crabtree effect in ascites hepatoma cells
Rodríguez‐Enríquez, S., Juárez, O. X., Rodríguez‐Zavala, J. S., & Moreno‐Sánchez, R. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.02140.x · Cited by 144 · see citing works
Parlo, R. A., & Coleman, P. S. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)90917-8 · Cited by 139 · see citing works
Immunoregulation by Parenteral Lipids: Impact of the n‐3 to n‐6 Fatty Acid Ratio
Grimm, H., Tibell, A., Norrlind, B., Blecher, C., Wilker, S., & Schwemmle, K. (1994) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607194018005417 · Cited by 132 · see citing works
Rosa, J. L., Casaroli-Marano, R. P., Buckler, A., Vilaró, S., & Barbacid, M. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00801.x · Cited by 130 · see citing works
Enzymes as RNA-binding proteins: a role for (di)nucleotide-binding domains?
Hentze, M. W. (1994) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(94)90198-8 · Cited by 128 · see citing works
Back to the roots: the remarkable RAF oncogene story
Zebisch, A., & Troppmair, J. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6005-y · Cited by 124 · see citing works
Witney, T. H., Kettunen, M. I., Day, S. E., Hu, D., Neves, A., Gallagher, F. A., Fulton, S. M., & Brindle, K. M. (2009) · Neoplasia · doi:10.1593/neo.09254 · Cited by 114 · see citing works
Carbonell, J., Marco, R., Felíu, J. E., & Sols, A. (1973) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1973.tb02969.x · Cited by 113 · see citing works
Boros, L. G., Lee, P. W. N., Brandes, J. L., Cascante, M., Muscarella, P., Schirmer, W. J., Melvin, W. S., & Ellison, E. C. (1998) · Medical Hypotheses · doi:10.1016/s0306-9877(98)90178-5 · Cited by 111 · see citing works
Glycolysis—one of the keys to cancer?
EIGENBRODT, E. (1980) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(80)90009-7 · Cited by 108 · see citing works
Mazurek, S., Zwerschke, W., Jansen‐Dürr, P., & EIGENBRODT, E. (2001) · Oncogene · doi:10.1038/sj.onc.1204792 · Cited by 107 · see citing works
Self-citationMazurek, S., Michel, A., & EIGENBRODT, E. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.8.4941 · Cited by 105 · see citing works
Self-citationWilliams, J. M., Chen, G. C., Zhu, L., & Rest, R. F. (1998) · Molecular Microbiology · doi:10.1046/j.1365-2958.1998.00670.x · Cited by 103 · see citing works
Cytosolic thyroid hormone-binding protein is a monomer of pyruvate kinase.
Kato, H., Fukuda, T., Parkison, C., McPhie, P., & Cheng, S.-Y. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.20.7861 · Cited by 99 · see citing works
Spoden, G. A., Rostek, U., Lechner, S. G., Mitterberger, M. C., Mazurek, S., & Zwerschke, W. (2009) · Experimental Cell Research · doi:10.1016/j.yexcr.2009.06.024 · Cited by 96 · see citing works
Self-citationRegulation of Cell Proliferation by Interleukin-3-induced Nuclear Translocation of Pyruvate Kinase
Hoshino, A., Hirst, J. A., & Fujii, H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700094200 · Cited by 94 · see citing works
Expression of hypoxia-inducible genes in tumor cells
Kress, S., Stein, A., Maurer, P., Weber, B., Reichert, J., Buchmann, A., Huppert, P. E., & Schwarz, M. (1998) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s004320050175 · Cited by 91 · see citing works
Yoo, B. C., Ku, J., Hong, S., Shin, Y., Park, S. Y., Kim, H. K., & Park, J. (2003) · International Journal of Cancer · doi:10.1002/ijc.11604 · Cited by 87 · see citing works
The Roles of PET and PET/CT in the Diagnosis and Management of Prostate Cancer
Takahashi, N., Inoue, T., Lee, J., Yamaguchi, T., & Shizukuishi, K. (2007) · Oncology · doi:10.1159/000112946 · Cited by 87 · see citing works
Bioenergetics of lung tumors: Alteration of mitochondrial biogenesis and respiratory capacity
Bellancé, N., Bénard, G., Furt, F., Bégueret, H., Smolková, K., Passerieux, E., Delage, J. P., Baste, J., Moreau, P., & Rossignol, R. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.08.012 · Cited by 85 · see citing works
Tumor type M2 pyruvate kinase expression in advanced breast cancer.
Lüftner, D., Mesterharm, J., Akrivakis, C., Geppert, R., Petrides, P. E., Wernecke, K.-D., & Possinger, K. (2000) · PubMed · Cited by 84 · see citing works
Miccheli, A., Tomassini, A., Puccetti, C., Valerio, M., Peluso, G., Tuccillo, F. M., Calvani, M., Manetti, C., & Conti, F. (2005) · Biochimie · doi:10.1016/j.biochi.2005.10.004 · Cited by 84 · see citing works
Schäfer, D., Hamm-Künzelmann, B., & Brand, K. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01314-8 · Cited by 84 · see citing works
Hacker, H. J. (1998) · Carcinogenesis · doi:10.1093/carcin/19.1.99 · Cited by 81 · see citing works
Schneider, J., Neu, K., Grimm, H., Velcovsky, H. G., Weisse, G., & EIGENBRODT, E. (2002) · PubMed · Cited by 79 · see citing works
Spoden, G. A., Mazurek, S., Morandell, D., Bacher, N., Ausserlechner, M. J., Jansen‐Dürr, P., EIGENBRODT, E., & Zwerschke, W. (2008) · International Journal of Cancer · doi:10.1002/ijc.23512 · Cited by 79 · see citing works
Self-citationPresek, P., Reinacher, M., & EIGENBRODT, E. (1988) · FEBS Letters · doi:10.1016/0014-5793(88)81014-7 · Cited by 79 · see citing works
L- and M2- pyruvate kinase expression in renal cell carcinomas and their metastases
Brinck, U., Fischer, G., EIGENBRODT, E., Oehmke, M. J., & Mazurek, S. (1994) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/bf00193498 · Cited by 77 · see citing works
Self-citationPotential Mechanisms for the Inhibition of Tumor Cell Growth by Manganese Superoxide Dismutase
Kim, K.-H., Rodriguez, A. M., Carrico, P. M., & Melendez, J. A. (2001) · Antioxidants and Redox Signaling · doi:10.1089/15230860152409013 · Cited by 77 · see citing works
The SUMO‐E3 ligase PIAS3 targets pyruvate kinase M2
Spoden, G. A., Morandell, D., Ehehalt, D., Fiedler, M., Jansen‐Dürr, P., Hermann, M., & Zwerschke, W. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22125 · Cited by 77 · see citing works
Loss of PKC-δ alters cardiac metabolism
Mayr, M., Chung, Y., Mayr, U., McGregor, E., Troy, H., Baier, G., Leitges, M., Dunn, M. J., Griffiths, J. R., & Xu, Q. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00877.2003 · Cited by 77 · see citing works
Mazurek, S. (2008) · Ernst Schering Research Foundation workshop/Ernst Schering Foundation Symposium proceedings · doi:10.1007/2789_2008_091 · Cited by 76 · see citing works
Self-citationTumour M2-pyruvate kinase: a gastrointestinal cancer marker
Kumar, Y., Tapuria, N., Kirmani, N., & Davidson, B. R. (2007) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0b013e3280102f78 · Cited by 76 · see citing works
Biochemical and Molecular Aspects of Selected Cancers
(1991) · Elsevier eBooks · doi:10.1016/c2013-0-11328-1 · Cited by 75 · see citing works
Takenaka, M., Noguchi, T., Inoue, H., Yamada, K., Matsuda, T., & Tanaka, T. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)94185-2 · Cited by 72 · see citing works
Shin, Y., Yoo, B. C., Hong, Y. S., Chang, H. J., Jung, K. H., Jeong, S., & Park, J. (2009) · Electrophoresis · doi:10.1002/elps.200800806 · Cited by 70 · see citing works
Marker for renal cell carcinoma (RCC): the dimeric form of pyruvate kinase type M2 (Tu M2-PK).
Wechsel, H. W., Petri, E., Bichler, K.-H., & Feil, G. (1999) · PubMed · Cited by 67 · see citing works
Tumor type M2 pyruvate kinase (TuM2‐PK) as a novel plasma tumor marker in melanoma
Ugurel, S., Bell, N. V. T., Sucker, A., Zimpfer, A., Rittgen, W., & Schadendorf, D. (2005) · International Journal of Cancer · doi:10.1002/ijc.21073 · Cited by 66 · see citing works
Martinez‐Balibrea, E., Plasencia, C., Ginés, A., Martínez‐Cardús, A., Musulén, E., Aguilera, R., Manzano, J. L., Neamati, N., & Abad, A. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0882 · Cited by 64 · see citing works
Ryll, T., & Wagner, R. (1992) · Biotechnology and Bioengineering · doi:10.1002/bit.260400810 · Cited by 62 · see citing works
Colorectal cancer screening by non-invasive metabolic biomarker fecal tumor M2-PK
Tonus, C. (2006) · World Journal of Gastroenterology · doi:10.3748/wjg.v12.i43.7007 · Cited by 61 · see citing works
Engel, M., Mazurek, S., EIGENBRODT, E., & Welter, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402768200 · Cited by 61 · see citing works
Self-citationExpression of pyruvate kinase M 2 in preneoplastic hepatic foci of N -nitrosomorpholine-treated rats
Steinberg, P., Klingelhöffer, A., Schäfer, A., Wüst, G., Weisse, G., Oesch, F., & EIGENBRODT, E. (1999) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s004280050330 · Cited by 60 · see citing works
Regulation of Pyruvate Kinase M Gene Expression
Yamada, K., & Noguchi, T. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0228 · Cited by 57 · see citing works
Tumor M2-PK and glutaminolytic enzymes in the metabolic shift of tumor cells.
Mazurek, S., Grimm, H., Oehmke, M. J., Weisse, G., Teigelkamp, S., & EIGENBRODT, E. (2000) · PubMed · Cited by 55 · see citing works
Self-citationPresek, P., Glossmann, H. H., EIGENBRODT, E., Schöner, W., Rübsamen, H., Friis, R. R., & Bauer, H. (1980) · PubMed · Cited by 54 · see citing works
Modulation of M2‐type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein
Shimada, N., Shinagawa, T., & Ishii, S. (2008) · Genes to Cells · doi:10.1111/j.1365-2443.2008.01165.x · Cited by 54 · see citing works
Regulation of pyruvate kinase type M2 by A-Raf: a possible glycolytic stop or go mechanism.
Mazurek, S., Drexler, H. C. A., Troppmair, J., EIGENBRODT, E., & Rapp, U. R. (2007) · PubMed · Cited by 53 · see citing works
Self-citationNetzker, R., Greiner, E. F., EIGENBRODT, E., Noguchi, T., Tanaka, T., & Brand, K. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42712-3 · Cited by 51 · see citing works
Duan, H., Hu, X.-W., Chen, J., Gao, L., Xi, Y.-Y., Lü, Y., Li, J., Zhao, S., Xu, J., Chen, H.-P., et al. (2007) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djm132 · Cited by 51 · see citing works
Netzker, R., Weigert, C., & Brand, K. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.00174.x · Cited by 49 · see citing works
Irminger‐Finger, I. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.10.8928 · Cited by 48 · see citing works
Weber, K., Ridderskamp, D., Alfert, M., Hoyer, S., & Wiesner, R. J. (2002) · Biological Chemistry · doi:10.1515/bc.2002.030 · Cited by 48 · see citing works
Regulation of glycolysis by Raf protein serine/threonine kinases
Mellay, V. L., Houben, R., Troppmair, J., Hagemann, C., Mazurek, S., Frey, U. H., Beigel, J., Weber, C. K., Benz, R., EIGENBRODT, E., et al. (2002) · Advances in Enzyme Regulation · doi:10.1016/s0065-2571(01)00036-x · Cited by 47 · see citing works
Self-citationA Multi-Functional Organelle Mitochondrion is Involved in Cell Death, Proliferation and Disease
Ohta, S. (2003) · Current Medicinal Chemistry · doi:10.2174/0929867033456440 · Cited by 47 · see citing works
Reinacher, M., & EIGENBRODT, E. (1981) · Virchows Archiv B Cell Pathology Including Molecular Pathology · doi:10.1007/bf02892557 · Cited by 46 · see citing works
Traxinger, R. R., & Marshall, S. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50150-8 · Cited by 46 · see citing works
Nutrient and hormonal regulation of pyruvate kinase gene expression
Yamada, K., & Noguchi, T. (1999) · Biochemical Journal · doi:10.1042/0264-6021:3370001 · Cited by 46 · see citing works
Allali‐Hassani, A., Wasney, G. A., Chau, I., Hong, B. S., Senisterra, G. A., Loppnau, P., Shi, Z., Moult, J., Edwards, A. M., Arrowsmith, C. H., et al. (2009) · Biochemical Journal · doi:10.1042/bj20090723 · Cited by 45 · see citing works
Kaura, B., Bagga, R., & Patel, F. D. (2004) · Journal of obstetrics and gynaecology research · doi:10.1111/j.1447-0756.2004.00187.x · Cited by 44 · see citing works
Spittler, A., Oehler, R., Goetzinger, P., Holzer, S., Reissner, C. M., Leutmezer, F., Rath, V., Wrba, F., Fuegger, R., Boltz‐Nitulescu, G., et al. (1997) · Journal of Nutrition · doi:10.1093/jn/127.11.2151 · Cited by 42 · see citing works
Traweger, A., Lehner, C., Farkas, A. E., Krizbai, I. A., Tempfer, H., Klement, É., Guenther, B., Bauer, H., & Bauer, H. (2007) · Differentiation · doi:10.1111/j.1432-0436.2007.00227.x · Cited by 42 · see citing works
Interaction between HERC1 and M2‐type pyruvate kinase
García-Gonzalo, F. R., Cruz, C., Muñoz, P., Mazurek, S., EIGENBRODT, E., Ventura, F., Bartrons, R., & Rosa, J. L. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00205-9 · Cited by 42 · see citing works
Self-citationSchäfer, D., Hamm-Künzelmann, B., Hermfisse, U., & Brand, K. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)00701-6 · Cited by 38 · see citing works
M2-PK as a novel marker in ovarian cancer. A prospective cohort study.
Ahmed, A. S., Dew, T. K., Lawton, F., Papadopoulos, A., Devaja, O., Raju, K. S., & Sherwood, R. A. (2007) · PubMed · Cited by 36 · see citing works
Alternative Splicing of the Pyruvate Kinase M Gene in a Minigene System
Takenaka, M., Yamada, K., Lu, T., Kang, R., Tanaka, T., & Noguchi, T. (1996) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1996.00366.x · Cited by 36 · see citing works
Metabolic characteristics of different malignant cancer cell lines.
Mazurek, S., Grimm, H., Wilker, S., Leib, S. L., & EIGENBRODT, E. (1998) · PubMed · Cited by 35 · see citing works
Self-citationThe dual activity of pyruvate kinase type M2 from chromatin extracts of neoplastic cells
Ignacak, J., & Stachurska, M. (2003) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/s1096-4959(02)00283-x · Cited by 34 · see citing works
Carbohydrate Metabolism and Neoplasia: New Perspectives for Diagnosis and Therapy
EIGENBRODT, E., Gerbracht, U., Mazurek, S., Presek, P., & Friis, R. R. (1994) · Elsevier eBooks · doi:10.1016/b978-0-12-564499-0.50014-6 · Cited by 34 · see citing works
Self-citationIsoform‐specific interaction of pyruvate kinase with hepatitis C virus NS5B
Wu, X., Zhou, Y., Zhang, K., Liu, Q., & Guo, D. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.05.033 · Cited by 33 · see citing works
Bannasch, P., Kanduc, D., Papa, S., & Tager, J. M. (2012) · Cited by 32 · see citing works
Burd, R., Wachsberger, P. R., Biaglow, J. E., Wahl, M., Lee, I., & Leeper, D. B. (2001) · PubMed · Cited by 31 · see citing works
Saheki, S., Harada, K., Sanno, Y., & Tanaka, T. (1978) · Biochimica et Biophysica Acta (BBA) - Enzymology · doi:10.1016/0005-2744(78)90296-6 · Cited by 31 · see citing works
EIGENBRODT, E., Fister, P., Rübsamen, H., & Friis, R. R. (1983) · The EMBO Journal · doi:10.1002/j.1460-2075.1983.tb01625.x · Cited by 29 · see citing works
Akhtar, K., Gupta, V., Koul, A., Alam, N., Bhat, R., & Bamezai, R. N. K. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808761200 · Cited by 29 · see citing works
M2-Pk As A Novel Marker In Ovarian Cancer, A Prospective Cohort Study
Ahmed, A. S., Dew, T. K., Papadopoulos, A., Devaja, O., Lawton, F., Raju, K. S., & Sherwood, R. A. (2006) · International Journal of Gynecological Cancer · doi:10.1136/ijgc-00009577-200610001-00264 · Cited by 26 · see citing works
Domingo, M., Einig, C., EIGENBRODT, E., & Reinacher, M. (1992) · Journal of Histochemistry & Cytochemistry · doi:10.1177/40.5.1374093 · Cited by 25 · see citing works
Huang, M. Q., NELSON, D. S., Pickup, S., Qiao, H., Delikatny, E. J., Poptani, H., & Glickson, J. D. (2007) · Academic Radiology · doi:10.1016/j.acra.2007.07.012 · Cited by 25 · see citing works
Mitochondrial disorders in renal tumors.
Hervouet, E., & Godinot, C. (2006) · Mitochondrion (Amsterdam. Print) · doi:10.1016/j.mito.2006.03.003 · Cited by 23 · see citing works
Double role of pyruvate kinase type M2 in the regulation of phosphometabolite pools
EIGENBRODT, E., Mazurek, S., & Friis, R. R. (1998) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-8950-6_2 · Cited by 22 · see citing works
Self-citationPyruvate Kinase in Selected Human Tumors
Staal, G. E. J., & Rijksen, G. (1991) · Elsevier eBooks · doi:10.1016/b978-0-12-564498-3.50013-3 · Cited by 22 · see citing works
The inhibitory effect of various fatty acids on aerobic glycolysis in Ehrlich ascites tumour cells.
Marchut, E., Guminska, M., & Kedryna, T. (1986) · PubMed · Cited by 22 · see citing works
Biochemical and Molecular Aspects of Selected Cancers
(1994) · Elsevier eBooks · doi:10.1016/c2009-0-02430-1 · Cited by 21 · see citing works
Interaction of melittin with a human lymphoblastoid cell line, HMy2
Weston, K. M., & Raison, R. L. (1998) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(19980201)68:2 · Cited by 19 · see citing works
Weernink, P. A. O., Rijksen, G., van der Heijden, M. C. M., & Staal, G. E. J. (1990) · PubMed · Cited by 19 · see citing works
Mitochondria in Health and Disease
Berdanier, C. D. (2005) · CRC Press eBooks · doi:10.1201/9781420028843 · Cited by 18 · see citing works
Insulin Stimulates Expression of the Pyruvate Kinase M Gene in 3T3-L1 Adipocytes
Asai, Y., Yamada, K., Watanabe, T., Keng, V. W., & Noguchi, T. (2003) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.67.1272 · Cited by 18 · see citing works
Use of a novel method to find substrates of protein kinase C delta identifies M2 pyruvate kinase
Siwko, S. K., & Mochly‐Rosen, D. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.01.018 · Cited by 18 · see citing works
Caleb, B. L., Hardenbrook, M. A., Cherington, V., & Castellot, J. J. (1996) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(199605)167:2 · Cited by 16 · see citing works
Self-citationImmunohistochemical localization of pyruvate kinase isoenzymes in chicken tissues
Reinacher, M., EIGENBRODT, E., Schering, B., & Schöner, W. (1979) · Histochemistry and Cell Biology · doi:10.1007/bf00490095 · Cited by 16 · see citing works
Elia, S., Massoud, R., Guggino, G., Cristino, B., Cortese, C., Massimi, A. R. D., & Zenobi, R. (2008) · European Journal of Cardio-Thoracic Surgery · doi:10.1016/j.ejcts.2008.01.014 · Cited by 16 · see citing works
Saheki, S., Saheki, K., & Tanaka, T. (2017) · Enzyme · doi:10.1159/000458623 · Cited by 14 · see citing works
Bannasch, P., Kanduc, D., Papa, S., & Tager, J. M. (1998) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-8950-6 · Cited by 14 · see citing works
Rodriguez‐Horche, P., Luque, J., Pérez-Artés, E., Pineda, M., & Pinilla, M. C. F. (1987) · Comparative Biochemistry and Physiology Part B Comparative Biochemistry · doi:10.1016/0305-0491(87)90051-4 · Cited by 9 · see citing works
Kroemer, G., Steger-Hartmann, T., Riefke, B., Petersen, K., Mumberg, D., & Keun, H. (2008) · Ernst Schering Research Foundation workshop/Ernst Schering Foundation Symposium proceedings · doi:10.1007/978-3-540-79478-3 · Cited by 6 · see citing works
Oxidative Phosphorylation Disease
Shoffner, J. M. (2005) · Oxidative stress and disease · doi:10.1201/9781420028843.ch4 · Cited by 6 · see citing works
Effects of tumor necrosis factor α (TNFα) on the phospholipid metabolism of Tetrahymena pyriformis
Kovacs, P. L., Kőhidai, L., & CSABA, G. (1998) · Cell Biochemistry and Function · doi:10.1002/(sici)1099-0844(199806)16:2 · Cited by 5 · see citing works
Oxidative Phosphorylation Disease: Diagnosis and Pathogenesis
Berdanier, C. D. (2005) · CRC Press eBooks · doi:10.1201/9781420028843-9 · Cited by 1 · see citing works
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Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate
Ward, P. S., & Thompson, C. B. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.014 · Cited by 3,233 · see citing works
Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation
Lunt, S. Y., & Vander Heiden, M. G. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154237 · Cited by 3,057 · see citing works
Targeting cancer metabolism: a therapeutic window opens
Heiden, M. G. V. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3504 · Cited by 1,409 · see citing works
Fueling Immunity: Insights into Metabolism and Lymphocyte Function
Pearce, E. L., Poffenberger, M. C., Chang, C.-H., & Jones, R. G. (2013) · Science · doi:10.1126/science.1242454 · Cited by 1,363 · see citing works
Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells
Maddocks, O. D. K., Berkers, C. R., Mason, S. M., Zheng, L., Blyth, K., Gottlieb, E., & Vousden, K. H. (2013) · Nature · doi:10.1038/nature11743 · Cited by 1,007 · see citing works
Serine and glycine metabolism in cancer
Amelio, I., Cutruzzolà, F., Antonov, A., Agostini, M., & Melino, G. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.004 · Cited by 1,056 · see citing works
Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation
Yang, W., Xia, Y., Ji, H., Zheng, Y., Liang, J., Huang, W., Gao, X., Aldape, K., & Lu, Z. (2011) · Nature · doi:10.1038/nature10598 · Cited by 1,033 · see citing works
Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis
Anastasiou, D., Yu, Y., Israelsen, W. J., Jiang, J.-K., Boxer, M. B., Hong, B. S., Tempel, W., Dimov, S., Shen, M., Jha, A., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1060 · Cited by 816 · see citing works
Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma
Feng, J., Li, J., Wu, L., Yu, Q., Ji, J., Wu, J., Dai, W., & Guo, C. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01629-4 · Cited by 698 · see citing works
Bonora, M., Patergnani, S., Rimessi, A., De Marchi, E., Suski, J. M., Bononi, A., Giorgi, C., Marchi, S., Missiroli, S., Poletti, F., et al. (2012) · Purinergic Signalling · doi:10.1007/s11302-012-9305-8 · Cited by 644 · see citing works
Pyruvate kinase: Function, regulation and role in cancer
Israelsen, W. J., & Heiden, M. G. V. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.08.004 · Cited by 599 · see citing works
Sun, Q., Chen, X., Ma, J., Peng, H., Wang, F., Zha, X., Wang, Y., Jing, Y., Yang, H., Chen, R., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014769108 · Cited by 586 · see citing works
2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents
Pająk, B., SİWİAK, E., Sołtyka, M., Priebe, A. M., Zielinski, R. J., Fokt, I., Ziemniak, M., Jaśkiewicz, A., Borowski, R., Domoradzki, T., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010234 · Cited by 574 · see citing works
PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells
Israelsen, W. J., Dayton, T. L., Davidson, S. M., Fiske, B. P., Hosios, A. M., Bellinger, G., Li, J., Yu, Y., Sasaki, M., Horner, J. W., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.025 · Cited by 549 · see citing works
PKM2, cancer metabolism, and the road ahead
Dayton, T. L., Jacks, T., & Vander Heiden, M. G. (2016) · The EMBO Reports · doi:10.15252/embr.201643300 · Cited by 515 · see citing works
A two-way street: reciprocal regulation of metabolism and signalling
Wellen, K. E., & Thompson, C. B. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3305 · Cited by 528 · see citing works
Choosing between glycolysis and oxidative phosphorylation: a tumor’s dilemma?
Jose, C., Bellance, N., & Rossignol, R. (2011) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.10.012 · Cited by 518 · see citing works
Alternative splicing and cancer: a systematic review
Zhang, Y., Qian, J., Gu, C., & Yang, Y. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00486-7 · Cited by 503 · see citing works
Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis
Zahra, K., Dey, T., Ashish, Mishra, S. P., & Pandey, U. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00159 · Cited by 507 · see citing works
PKM2, function and expression and regulation
Zhang, Z., Deng, X., Liu, Y., Liu, Y., Sun, L., & Chen, F. (2019) · Cell & Bioscience · doi:10.1186/s13578-019-0317-8 · Cited by 501 · see citing works
Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch
Gubser, P. M., Bantug, G. R., Razik, L., Fischer, M., Dimeloe, S., Höenger, G., Müller-Durovic, B., Jauch, A., & Hess, C. (2013) · Nature Immunology · doi:10.1038/ni.2687 · Cited by 487 · see citing works
Metabolic checkpoints in activated T cells
Wang, R., & Green, D. R. (2012) · Nature Immunology · doi:10.1038/ni.2386 · Cited by 457 · see citing works
Anticancer Targets in the Glycolytic Metabolism of Tumors: A Comprehensive Review
Porporato, P. E., Dhup, S., Dadhich, R. K., Copetti, T., & Sonveaux, P. (2011) · Frontiers in Pharmacology · doi:10.3389/fphar.2011.00049 · Cited by 424 · see citing works
Ye, J., Mancuso, A., Tong, X., Ward, P. S., Fan, J., Rabinowitz, J. D., & Thompson, C. B. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1204176109 · Cited by 410 · see citing works
Emerging roles of PKM2 in cell metabolism and cancer progression
Luo, W., & Semenza, G. L. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.06.010 · Cited by 380 · see citing works
The metabolic function of cyclin D3-CDK6 kinase in cancer cell survival
Wang, H., Nicolay, B. N., Chick, J. M., Gao, X., Geng, Y., Ren, H., Gao, H., Yang, G., Williams, J. A., Suski, J. M., et al. (2017) · Nature · doi:10.1038/nature22797 · Cited by 347 · see citing works
PKM2 contributes to cancer metabolism
Wong, N., Ojo, D., Yan, J., & Tang, D. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.01.031 · Cited by 349 · see citing works
Lv, L., Xu, Y.-P., Zhao, D., Li, F.-L., Wang, W., Sasaki, N., Jiang, Y., Zhou, X., Li, T.-T., Guan, K., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.09.004 · Cited by 335 · see citing works
The role of the HIF‐1α/ALYREF/PKM2 axis in glycolysis and tumorigenesis of bladder cancer
Wang, J., Zhu, W., Han, J., Yang, X. F., Zhou, R., Lu, H., Yu, H., Yuan, W., Li, P., Tao, J., et al. (2021) · 癌症:英文版 · doi:10.1002/cac2.12158 · Cited by 317 · see citing works
Dysregulated metabolism contributes to oncogenesis
Hirschey, M. D., DeBerardinis, R. J., Diehl, A. M., Drew, J. E., Frezza, C., Green, M. F., Jones, L. W., Ko, Y. H., Le, A., Lea, M. A., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.10.002 · Cited by 306 · see citing works
JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1α–mediated glucose metabolism
Wang, H., Hsieh, Y., Cheng, W.-C., Lin, C.-P., Lin, Y.-S., Yang, S.-F., Chen, C.-C., Izumiya, Y., Yu, J., Kung, H.-J., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1311249111 · Cited by 306 · see citing works
Metabolic Pathway Alterations that Support Cell ProliferationPreprint
Heiden, M. G. V., Lunt, S. Y., Dayton, T. L., Fiske, B. P., Israelsen, W. J., Mattaini, K. R., Vokes, N. I., Stephanopoulos, G. N., Cantley, L. C., Metallo, C. M., et al. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2012.76.010900 · Cited by 300 · see citing works
Rocking cell metabolism: revised functions of the key glycolytic regulator PKM2 in cancer
Chaneton, B., & Gottlieb, E. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.04.003 · Cited by 294 · see citing works
Agnihotri, S., & Zadeh, G. M. (2015) · Neuro-Oncology · doi:10.1093/neuonc/nov125 · Cited by 294 · see citing works
Pkm2 Regulates Cardiomyocyte Cell Cycle and Promotes Cardiac Regeneration
Magadum, A., Singh, N., Kurian, A. A., Munir, I., Mehmood, T., Brown, K., Sharkar, M. T. K., Chepurko, E., Sassi, Y., Oh, J. G., et al. (2020) · Circulation · doi:10.1161/circulationaha.119.043067 · Cited by 287 · see citing works
Xu, Q., Tu, J., Dou, C., Zhang, J., Yang, L., Liu, X., Lei, K., Liu, Z., Wang, Y., Li, L., et al. (2017) · Molecular Cancer · doi:10.1186/s12943-017-0748-y · Cited by 284 · see citing works
The Influence of Metabolism on Drug Response in Cancer
Zaal, E. A., & Berkers, C. R. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00500 · Cited by 272 · see citing works
Pyruvate kinase M2 (PKM2) in cancer and cancer therapeutics
Zhu, S., Guo, Y., Zhang, X., Liu, H., Yin, M., Chen, X., & Peng, C. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.11.018 · Cited by 271 · see citing works
Liao, M., Yao, D., Wu, L., Luo, C., Wang, Z., Zhang, J., & Liu, B. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.12.003 · Cited by 280 · see citing works
Lim, S., Li, C., Xia, W., Lee, H., Chang, S.-S., Shen, J., Hsu, J. L., Raftery, D., Djukovic, D., Gu, H., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2478 · Cited by 263 · see citing works
Tedeschi, P. M., Markert, E. K., Gounder, M. K., Lin, H., Dvorzhinski, D., Dolfi, S. C., Chan, L. L.-Y., Qiu, J., DiPaola, R. S., Hirshfield, K. M., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.393 · Cited by 261 · see citing works
Pyruvate Kinase Isoform Expression Alters Nucleotide Synthesis to Impact Cell Proliferation
Lunt, S. Y., Muralidhar, V., Hosios, A. M., Israelsen, W. J., Gui, D. Y., Newhouse, L., Ogrodzinski, M. P., Hecht, V. C., Xu, K., Acevedo, P. N. M., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.10.027 · Cited by 259 · see citing works
PKM2, a Central Point of Regulation in Cancer Metabolism
Wong, N., Melo, J. D., & Tang, D. (2013) · International Journal of Cell Biology · doi:10.1155/2013/242513 · Cited by 243 · see citing works
Metabolic rearrangements in primary liver cancers: cause and consequences
Satriano, L., Lewińska, M., Rodrigues, P. M., Bañales, J. M., & Andersen, J. B. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0217-8 · Cited by 241 · see citing works
Billiard, J., Dennison, J. B., Briand, J., Annan, R. S., Chai, D., Colón, M., Dodson, C. S., Gilbert, S. A., Greshock, J. D., Jing, J., et al. (2013) · Cancer & Metabolism · doi:10.1186/2049-3002-1-19 · Cited by 242 · see citing works
Pyruvate Kinase M2: Multiple Faces for Conferring Benefits on Cancer Cells
Tamada, M., Suematsu, M., & Saya, H. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0859 · Cited by 239 · see citing works
Chen, M., Zhang, J., & Manley, J. L. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2513 · Cited by 237 · see citing works
Pyruvate kinase M2-specific siRNA induces apoptosis and tumor regression
Goldberg, M. S., & Sharp, P. A. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20111487 · Cited by 232 · see citing works
Lactate promotes glutamine uptake and metabolism in oxidative cancer cells
Pérez-Escuredo, J., Dadhich, R. K., Dhup, S., Cacace, A., Van Hée, V. F., De Saedeleer, C. J., Sboarina, M., Rodriguez, F., Fontenille, M.-J., Brisson, L., et al. (2016) · Cell Cycle · doi:10.1080/15384101.2015.1120930 · Cited by 231 · see citing works
Lactate Dehydrogenase B Controls Lysosome Activity and Autophagy in Cancer
Brisson, L., Bański, P., Sboarina, M., Dethier, C., Danhier, P., Fontenille, M., Hée, V. F. V., Vazeille, T., Tardy, M., Falces, J., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.08.005 · Cited by 226 · see citing works
Keller, K. E., Tan, I. S., & Lee, Y.-S. (2012) · Science · doi:10.1126/science.1224409 · Cited by 228 · see citing works
Grasso, D., Zampieri, L. X., Capelôa, T., de Velde, J. A. V., & Sonveaux, P. (2020) · Cell Stress · doi:10.15698/cst2020.06.221 · Cited by 231 · see citing works
Ma, Y., Huang, J., Han, T., Yan, C., Cao, C., & Cao, M. (2021) · Water Research · doi:10.1016/j.watres.2021.117420 · Cited by 228 · see citing works
Payen, V. L., Porporato, P. E., Baselet, B., & Sonveaux, P. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2098-5 · Cited by 219 · see citing works
van den Heuvel, A. P. J., Jing, J., Wooster, R. F., & Bachman, K. E. (2012) · Cancer Biology & Therapy · doi:10.4161/cbt.21348 · Cited by 209 · see citing works
How do glycolytic enzymes favour cancer cell proliferation by nonmetabolic functions?
Lincet, H., & Icard, P. (2014) · Oncogene · doi:10.1038/onc.2014.320 · Cited by 207 · see citing works
How does cancer cell metabolism affect tumor migration and invasion?
Han, T., Kang, D., Ji, D., Wang, X., Zhan, W., Fu, M., Xin, H.-B., & Wang, J.-B. (2013) · Cell Adhesion & Migration · doi:10.4161/cam.26345 · Cited by 198 · see citing works
Targeting Bacterial Central Metabolism for Drug Development
Murima, P., McKinney, J. D., & Pethe, K. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.08.020 · Cited by 190 · see citing works
Diverting Glycolysis to Combat Oxidative Stress
Mullarky, E., & Cantley, L. C. (2015) · Springer eBooks · doi:10.1007/978-4-431-55651-0_1 · Cited by 190 · see citing works
Pyruvate kinase M2 and cancer: an updated assessment
Iqbal, M. A., Gupta, V., Prakasam, G., Mazurek, S., & Bamezai, R. N. K. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.04.011 · Cited by 189 · see citing works
Self-citationZheng, J., Xie, Y., Ren, L., Qi, L., Wu, L., Pan, X., Zhou, J., Zhou, C., & Liu, L. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101180 · Cited by 190 · see citing works
Regulation and function of pyruvate kinase M2 in cancer
Yang, W., & Lu, Z. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.06.008 · Cited by 182 · see citing works
M2 pyruvate kinase provides a mechanism for nutrient sensing and regulation of cell proliferation
Morgan, H. P., O’Reilly, F. J., Wear, M. A., O’Neill, J. R., Fothergill‐Gilmore, L. A., Hupp, T. R., & Walkinshaw, M. D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217157110 · Cited by 182 · see citing works
Hsu, M., & Hung, W. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0791-3 · Cited by 180 · see citing works
Keller, K. E., Doctor, Z. M., Dwyer, Z. W., & Lee, Y. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.02.015 · Cited by 179 · see citing works
The multifaceted regulation and functions of PKM2 in tumor progression
Li, Z., Yang, P., & Li, Z. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.07.008 · Cited by 175 · see citing works
Metabolic rewiring in melanoma
Ratnikov, B. I., Scott, D. A., Osterman, A. L., Smith, J. W., & Ronai, Z. A. (2016) · Oncogene · doi:10.1038/onc.2016.198 · Cited by 168 · see citing works
Anticancer Agents That Counteract Tumor Glycolysis
Granchi, C., & Minutolo, F. (2012) · ChemMedChem · doi:10.1002/cmdc.201200176 · Cited by 166 · see citing works
One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy
Shuvalov, O., Petukhov, A., Daks, A., Fedorova, O., Vasileva, E., & Barlev, N. A. (2017) · Oncotarget · doi:10.18632/oncotarget.15053 · Cited by 168 · see citing works
Understanding the central role of citrate in the metabolism of cancer cells
Icard, P., Poulain, L., & Lincet, H. (2011) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2011.10.007 · Cited by 162 · see citing works
Therapeutic targeting of glutaminolysis as an essential strategy to combat cancer
Matés, J. M., Paola, F. J. D., Campos-Sandoval, J. A., Mazurek, S., & Márquez, J. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.012 · Cited by 164 · see citing works
Self-citationGardner, D. K., & Harvey, A. J. (2015) · Reproduction Fertility and Development · doi:10.1071/rd14421 · Cited by 162 · see citing works
M2 isoform of pyruvate kinase is dispensable for tumor maintenance and growth
Cortés-Cros, M., Hemmerlin, C., Ferretti, S., Zhang, J., Gounarides, J. S., Yin, H., Muller, A., Haberkorn, A., Chene, P., Sellers, W. R., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1212780110 · Cited by 159 · see citing works
Analysis of metabolism to select viable human embryos for transfer
Gardner, D. K., & Wale, P. L. (2013) · Fertility and Sterility · doi:10.1016/j.fertnstert.2012.12.004 · Cited by 158 · see citing works
Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinomaPreprint
Dayton, T. L., Gocheva, V., Miller, K. M., Israelsen, W. J., Bhutkar, A. J., Clish, C. B., Davidson, S. M., Luengo, A., Bronson, R. T., Jacks, T., et al. (2016) · Genes & Development · doi:10.1101/gad.278549.116 · Cited by 158 · see citing works
Posttranslational Modifications of Pyruvate Kinase M2: Tweaks that Benefit Cancer
Prakasam, G., Iqbal, M. A., Bamezai, R. N. K., & Mazurek, S. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00022 · Cited by 156 · see citing works
Self-citationSIRT6 deacetylates PKM2 to suppress its nuclear localization and oncogenic functions
Bhardwaj, A., & Das, S. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520045113 · Cited by 154 · see citing works
Rosa, V. D., Iommelli, F., Monti, M., Fonti, R., Votta, G., Stoppelli, M. P., & Vecchio, S. D. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0375 · Cited by 150 · see citing works
The metabolic landscape of lung cancer: New insights in a disturbed glucose metabolism
Vanhove, K., Graulus, G.-J., Mesotten, L., Thomeer, M., Derveaux, E., Noben, J.-P., Guedens, W., & Adriaensens, P. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01215 · Cited by 147 · see citing works
The P2X7 receptor is a key modulator of aerobic glycolysis
Amoroso, F., Falzoni, S., Adinolfi, E., Ferrari, D., & Virgilio, F. D. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.105 · Cited by 145 · see citing works
Park, S., Özden, Ö., Liu, G., Song, H. Y., Zhu, Y., Yan, Y., Zou, X., Kang, H.-J., Jiang, H., Principe, D. R., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2498 · Cited by 144 · see citing works
Luan, W., Wang, Y., Chen, X., Shi, Y., Wang, J., Zhang, J., Qian, J., Li, R., Tao, T., Wei, W., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3514 · Cited by 143 · see citing works
Effect of posttranslational modifications on enzyme function and assembly
Ryšlavá, H., Hýsková, V., Kavan, D., & Vaněk, O. (2013) · Journal of Proteomics · doi:10.1016/j.jprot.2013.03.025 · Cited by 142 · see citing works
Pyruvate kinase M2 facilitates colon cancer cell migration via the modulation of STAT3 signalling
Yang, P., Li, Z., Fu, R., Wu, H., & Li, Z. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.03.020 · Cited by 138 · see citing works
Sun, K., Tang, S., Hou, Y., Xi, L., Chen, Y., Yin, J., Peng, M., Zhao, M., Cui, X., & Liu, M. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.02.025 · Cited by 138 · see citing works
Targeting the ATF4 pathway in cancer therapy
Singleton, D. C., & Harris, A. L. (2012) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2012.728207 · Cited by 130 · see citing works
Vallée, A., Guillevin, R., & Vallée, J.-N. (2017) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0032 · Cited by 134 · see citing works
Fructose 2,6-Bisphosphate in Cancer Cell Metabolism
Bartrons, R., Simon‐Molas, H., Rodríguez‐García, A., Castaño, E., Navarro‐Sabaté, À., Manzano, À., & Martinez‐Outschoorn, U. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00331 · Cited by 134 · see citing works
Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins
Chen, M., David, C. J., & Manley, J. L. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2219 · Cited by 132 · see citing works
Bladder Cancer Biomarker Discovery Using Global Metabolomic Profiling of Urine
Wittmann, B. M., Stirdivant, S. M., Mitchell, M. W., Wulff, J. E., McDunn, J. E., Li, Z., Dennis-Barrie, A., Neri, B. P., Milburn, M. V., Lotan, Y., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115870 · Cited by 132 · see citing works
Targeting aerobic glycolysis: 3-bromopyruvate as a promising anticancer drug
Cardaci, S., Desideri, E., & Ciriolo, M. R. (2012) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-012-9422-7 · Cited by 132 · see citing works
Metabolic Reprogramming in Brain Tumors
Venneti, S., & Thompson, C. B. (2017) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044329 · Cited by 131 · see citing works
Icard, P., & Lincet, H. (2012) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2012.07.001 · Cited by 123 · see citing works
Amin, S., Yang, P., & Li, Z. (2019) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2019.02.003 · Cited by 126 · see citing works
Allosteric Regulation of PKM2 Allows Cellular Adaptation to Different Physiological States
Gui, D. Y., Lewis, C. A., & Heiden, M. G. V. (2013) · Science Signaling · doi:10.1126/scisignal.2003925 · Cited by 123 · see citing works
Alterations of metabolic genes and metabolites in cancer
Oermann, E. K., Wu, J., Guan, K., & Xiong, Y. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.01.013 · Cited by 122 · see citing works
Canto, A. C. V. D. C. S., Suman, S. P., Nair, M. N., Li, S., Rentfrow, G. K., Beach, C. M., Silva, T. J. P., WHEELER, T. L., Shackelford, S. D., Grayson, A. L., et al. (2014) · Meat Science · doi:10.1016/j.meatsci.2014.11.011 · Cited by 119 · see citing works
PKM2 promotes pulmonary fibrosis by stabilizing TGF-β1 receptor I and enhancing TGF-β1 signaling
Gao, S., Li, X., Jiang, Q., Liang, Q. L., Zhang, F., Li, S., Zhang, R., Luan, J., Zhu, J., Gu, X., et al. (2022) · Science Advances · doi:10.1126/sciadv.abo0987 · Cited by 119 · see citing works
Yang, L., Hou, Y., Yuan, J., Tang, S., Zhang, H., Zhu, Q., Du, Y.-E., Zhou, M., Wen, S., Xu, L., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4697 · Cited by 115 · see citing works
Advances in Hypoxia-Mediated Mechanisms in Hepatocellular Carcinoma
Xiong, X., Qiu, X. Y., Hu, D. X., & Chen, X. (2017) · Molecular Pharmacology · doi:10.1124/mol.116.107706 · Cited by 118 · see citing works
- Authors
- Mazurek, S.
- Affiliations
- Justus-Liebig-Universität Gießen (DE)
- Corresponding author
- Mazurek, Sybille
- ORCID
- Mazurek, Sybille
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 43
- Issue
- 7
- Pages
- 969-980
- ISSN
- 1357-2725 (ISSN-L)
- OpenAlex
- W2029255902
- Cited by
- 694
- References
- 146
- Citations by year
- 2026: 14 · 2025: 41 · 2024: 39 · 2023: 46 · 2022: 35 · 2021: 52 · 2020: 35 · 2019: 42 · 2018: 52 · 2017: 46 · 2016: 41 · 2015: 63 · 2014: 50 · 2013: 60 · 2012: 49
- FWCI
- 13.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The International Journal of Biochemistry & Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- PKM2, cancer metabolism, Warburg effect, glycolysis, transcriptional regulation, phosphotyrosine peptides, metabolic intermediates, tumor markers, nuclear translocation, apoptosis, cell proliferation, therapeutic target
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Glucose, Glutamine, Glycolysis, Humans, Isoenzymes, Models, Biological, Neoplasm Proteins, Neoplasms, Pyruvate Kinase, Biomarkers, Tumor, Oncogene Proteins, Protein Serine-Threonine Kinases, Tumor Suppressor Proteins, Protein Interaction Mapping, Cell Proliferation, Octamer Transcription Factor-3, Mice, Rats, Metabolic Networks and Pathways
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