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Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis
Open accessAbstract
Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. The interaction of PKM2 with phosphotyrosine-containing proteins inhibits enzyme activity and increases the availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small-molecule PKM2 activators inhibits the growth of xenograft tumors. Structural studies reveal that small-molecule activators bind PKM2 at the subunit interaction interface, a site that is distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. These data support the notion that small-molecule activation of PKM2 can interfere with anabolic metabolism.
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“Indeed, activation of pyruvate kinase can inhibit cancer cell proliferation and tumor growth in some settings (Anastasiou et al., 2012; Kung et al., 2012; Walsh et al., 2010), but because pyruvate kinase expression is dispensable for the growth of some tumors (Cortes-Cros et al., 2013; Israelsen et al., 2013), whether pyruvate kinase activation will lead to durable responses remains an area of”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Anastasiou et al., 2012
In the citing paper
“Activating PKM2 by using small-molecule agonists increases PEP-to-pyruvate conversion, reducing the flux of glycolytic intermediates toward anabolic pathways and slowing tumor cell growth (56, 60).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [56]
In the citing paper
“PKM2 exists as either an inactive dimer or an active tetramer, and oscillation between these two states influences the ability of cells to maintain anabolic metabolism (56).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [56]
In the citing paper
“In order to examine the functional relevance of PKM2 for LPS action we next examined the effect of two highly specific small-molecule PKM2 activators, TEPP-46 and DASA-58.”
From Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages (2015) · cites this paper as Anastasiou et al., 2012
In the citing paper
“TEPP-46, but not DASA-58, is pharmacokinetically validated in vivo (Anastasiou et al., 2012).”
From Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages (2015) · cites this paper as Anastasiou et al., 2012
In the citing paper
“These well-characterized and highly specific compounds bind PKM2, which then forms a tight tetramer with PKM1-like kinetic properties, an event that is resistant to inhibition by tyrosine phosphorylation.”
From Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages (2015) · cites this paper as Anastasiou et al., 2012
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Citations
Cites
Berman, H. M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.235 · Cited by 40,196
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 29,915
Colowick, S. P., Joshi, M. D., Jagannathan, & KAPLAN, N. O. (1966) · Cited by 26,137
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Self-citationRefinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,796
Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?
Trachootham, D., Alexandre, J., & Huang, P. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2803 · Cited by 5,452
PRODRG: a tool for high-throughput crystallography of protein–ligand complexes
Schüttelkopf, A. W., & van Aalten, D. M. F. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904011679 · Cited by 4,837
Regulation of cancer cell metabolism
Cairns, R. A., Harris, I. S., & Mak, T. W. (2011) · Nature Reviews Cancer · doi:10.1038/nrc2981 · Cited by 4,744
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
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Zhong, W., Liang, C., Goh, B. C., Cai, Q., Ho, P., Chionh, Y. H., Yuan, M., Sahili, A. E., Fothergill‐Gilmore, L. A., Walkinshaw, M. D., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02086-y · Cited by 66
An allostatic mechanism for M2 pyruvate kinase as an amino-acid sensor
Yuan, M., McNae, I. W., Chen, Y., Blackburn, E. A., Wear, M. A., Michels, P. A. M., Fothergill‐Gilmore, L. A., Hupp, T. R., & Walkinshaw, M. D. (2018) · Biochemical Journal · doi:10.1042/bcj20180171 · Cited by 70
Wu, D., Dasgupta, A., Read, A. D., Bentley, R. E. T., Motamed, M., Chen, K., Al‐Qazazi, R., Mewburn, J. D., Dunham‐Snary, K. J., Alizadeh, E., et al. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.12.452 · Cited by 69
Reversible amyloids of pyruvate kinase couple cell metabolism and stress granule disassembly
Cereghetti, G., Wilson-Zbinden, C., Kissling, V. M., Diether, M., Arm, A., Yoo, H., Piazza, I., Saad, S., Picotti, P., Drummond, D. A., et al. (2021) · Nature Cell Biology · doi:10.1038/s41556-021-00760-4 · Cited by 64
Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm
Liu, Z., Le, Y., Chen, H., Zhu, J., & Lu, D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.748573 · Cited by 66
Granja, S., Marchiq, I., LeFloch, R., Moura, C. S., Baltazar, F., & Pouysségur, J. (2014) · Oncotarget · doi:10.18632/oncotarget.2862 · Cited by 64
Loss of DJ-1 impairs antioxidant response by altered glutamine and serine metabolism
Meiser, J., Delcambre, S., Wegner, A., Jäger, C., Ghelfi, J., d’Hérouël, A. F., Dong, X., Weindl, D., Stautner, C., Nonnenmacher, Y., et al. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.01.019 · Cited by 66
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Liu, F., Ma, M., Gao, A., Ma, F., Ma, G., Liu, P., Jia, C., Wang, Y., Donahue, K., Zhang, S., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108065 · Cited by 64
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Stanke, K. M., Wilson, C., & Kidambi, S. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.752404 · Cited by 64
Icard, P., Simula, L., Fournel, L., Leroy, K., Mansuet‐Lupo, A., Damotte, D., Charpentier, M.-C., Durdux, C., Loi, M., Schussler, O., et al. (2022) · Drug Resistance Updates · doi:10.1016/j.drup.2022.100852 · Cited by 63
Gao, L., Yang, F., Tang, D., Xu, Z., Tang, Y., Yang, D., Sun, D., Chen, Z., & Teng, Y. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02574-0 · Cited by 68
Koufaris, C., Valbuena, G. N., Pomyen, Y., Tredwell, G. D., Nevedomskaya, E., Lau, C.-H., Yang, T.-Y., Benito, A., Ellis, J. K., & Keun, H. C. (2015) · Oncogene · doi:10.1038/onc.2015.333 · Cited by 64
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Milne, S. B., Mathews, T. P., Myers, D. S., Ivanova, P. T., & Brown, H. A. (2013) · Biochemistry · doi:10.1021/bi400060e · Cited by 65
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He, X., Du, S., Lei, T., Li, X., Liu, Y., Wang, H., Tong, R., & Wang, Y. (2017) · Oncotarget · doi:10.18632/oncotarget.22529 · Cited by 63
Ren, R., Guo, J., Shi, J. Y., Tian, Y., Li, M., & Kang, H. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29549 · Cited by 62
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Apostolidi, M., Vathiotis, I. A., Muthusamy, V., Gaule, P., Gassaway, B. M., Rimm, D. L., & Rinehart, J. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-4190 · Cited by 65
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Tian, Y., Wan, N., Zhang, H., Shao, C., Ding, M., Bao, Q., Hu, H., Sun, H., Liu, C., Zhou, K., et al. (2023) · Nature Chemical Biology · doi:10.1038/s41589-023-01355-w · Cited by 64
Natural Compounds as Regulators of the Cancer Cell Metabolism
Cerella, C., Radogna, F., Dicato, M. A., & Diederich, M. F. (2013) · International Journal of Cell Biology · doi:10.1155/2013/639401 · Cited by 67
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Gabizon, R., & Friedler, A. (2014) · Frontiers in Chemistry · doi:10.3389/fchem.2014.00009 · Cited by 63
Zhu, J., Chen, H., Le, Y., Guo, J., Liu, Z., Dou, X., & Lu, D. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1009229 · Cited by 63
Papadaki, C., Sfakianaki, M., Lagoudaki, E. D., Giagkas, G., Ioannidis, G., Trypaki, M., Tsakalaki, E., Voutsina, A., Koutsopoulos, A. V., Mavroudis, D., et al. (2014) · British Journal of Cancer · doi:10.1038/bjc.2014.492 · Cited by 61
The Crabtree and Warburg effects: Do metabolite-induced regulations participate in their induction?
Hammad, N., Rosas‐Lemus, M., Uribe‐Carvajal, S., Rigoulet, M., & Devin, A. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.03.034 · Cited by 61
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Jin, X., Zhang, W., Wang, Y., Liu, J., Hao, F., Li, Y., Tian, M., Shu, H., Dong, J., Feng, Y., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107690 · Cited by 61
O'Rourke, S. A., Neto, N. G. B., Devilly, E., Shanley, L. C., Fitzgerald, H. K., Monaghan, M. G., & Dunne, A. (2022) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2022.05.015 · Cited by 62
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Ding, Y., Xue, Q., Liu, S., Hu, K., Wang, D., Wang, T., Li, Y., Guo, H., Hao, X., Ge, W., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01328 · Cited by 58
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Warner, S. L., Carpenter, K. J., & Bearss, D. J. (2014) · Future Medicinal Chemistry · doi:10.4155/fmc.14.70 · Cited by 57
Filipp, F. V. (2013) · Journal of Carcinogenesis · doi:10.4103/1477-3163.115423 · Cited by 59
Patsoukis, N., Weaver, J. D., Strauss, L., Herbel, C., Seth, P., & Boussiotis, V. A. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00330 · Cited by 57
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Chao, T., Huang, T., Liao, Y.-P., Huang, R., Su, P., Shen, H.-Y., Lai, H., & Wang, Y.-C. (2017) · PLoS ONE · doi:10.1371/journal.pone.0182166 · Cited by 55
Nagasawa, I., Muroi, M., Kawatani, M., Ohishi, T., Ohba, S., Kawada, M., & Osada, H. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.11.010 · Cited by 54
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Gao, J., & Chen, Y. (2015) · BioMed Research International · doi:10.1155/2015/354143 · Cited by 55
Guo, D., Gu, J., Jiang, H., Ahmed, A., Zhang, Z., & Gu, Y. (2016) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2016.01.009 · Cited by 53
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Liang, F., Li, Q., Li, X., Li, Z., Gong, Z., Deng, H., Xiang, B., Zhou, M., Li, X., Li, G., et al. (2016) · International Journal of Oncology · doi:10.3892/ijo.2016.3599 · Cited by 53
Pei, L., Le, Y., Chen, H., Feng, J., Liu, Z., Zhu, J., Wang, C., Chen, L., Dou, X., & Lu, D. (2021) · Fitoterapia · doi:10.1016/j.fitote.2021.104922 · Cited by 52
Satyanarayana, G., Turaga, R. C., Sharma, M., Wang, S., Mishra, F., Peng, G., Deng, X., Yang, J. J., & Liu, Z. (2021) · Theranostics · doi:10.7150/thno.60385 · Cited by 52
Tech, K., Tikunov, A. P., Farooq, H., Morrissy, A. S., Meidinger, J., Fish, T., Green, S. C., Liu, H., Li, Y., Mungall, A. J. J., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-3304 · Cited by 51
Wu, Y.-H., Yang, Y., Chen, C.-H., Hsiao, C.-J., Li, T., Liao, K.-J., Watashi, K., Chen, B., & Wang, L. H.-C. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1008866 · Cited by 51
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Yang, P., Ding, G., Liu, W., Fu, R., Amin, S., & Li, Z. (2018) · Food & Function · doi:10.1039/c8fo01161c · Cited by 51
Guo, J., Xue, Q., Liu, K., Ge, W., Liu, W., Wang, J., Zhang, M., Li, Q., Cai, D. D., Shan, C., et al. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00993 · Cited by 51
Foster, H. R., Ho, T., Potapenko, E. S., Sdao, S. M., Huang, S. M., Lewandowski, S. L., VanDeusen, H. R., Davidson, S. M., CARDONE, R. L., Prentki, M., et al. (2022) · eLife · doi:10.7554/elife.79422 · Cited by 54
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Mu, Y., Chen, Y., Zhang, G., Zhan, X., Li, Y., Liu, T., Li, G., Li, M., Xiao, Z., Gong, X., et al. (2013) · Electrophoresis · doi:10.1002/elps.201200596 · Cited by 49
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Fukuda, S., Miyata, H., Miyazaki, Y., Makino, T., Takahashi, T., Kurokawa, Y., Yamasaki, M., Nakajima, K., Takiguchi, S., Mori, M., et al. (2015) · Annals of Surgical Oncology · doi:10.1245/s10434-015-4522-3 · Cited by 45
Zhao, P., Han, S.-N., Arumugam, S., Yousaf, M. N., Qin, Y., Jiang, J. X., Torok, N. J., Chen, Y., Mankash, M. S., Liu, J., et al. (2019) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00054.2019 · Cited by 45
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Metadata
- Authors
- Anastasiou, D., Yu, Y., Israelsen, W. J., Jiang, J.-K., Boxer, M. B., Hong, B. S., Tempel, W., Dimov, S., Shen, M., Jha, A., Yang, H., Mattaini, K. R., Metallo, C. M., Fiske, B. P., Courtney, K. D., Malstrom, S., Khan, T. M., Kung, C., Skoumbourdis, A. P., Veith, H., Southall, N., Walsh, M. J., Brimacombe, K. R., Leister, W., Lunt, S. Y., Johnson, Z. R., Yen, K. E., Kunii, K., Davidson, S. M., Christofk, H. R., Austin, C. P., Inglese, J., Harris, M. H., Asara, J. M., Stephanopoulos, G., Salituro, F. G., Jin, S., Dang, L., Auld, D. S., Park, H.-W., Cantley, L. C., Thomas, C. J., & Vander Heiden, M. G.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Massachusetts Institute of Technology (US)
- National Institutes of Health (US)
- University of Toronto (CA)
- Agios Pharmaceuticals (United States) (US)
- University of California San Diego (US)
- Boston Children's Hospital (US)
- ORCID
- Anastasiou, Dimitrios
- Yu, Yimin
- Israelsen, William J
- Jiang, Jian-Kang
- Tempel, Wolfram
- Shen, Min
- Jha, Abhishek
- Yang, Hua
- Mattaini, Katherine R
- Metallo, Christian M
- Fiske, Brian P
- Courtney, Kevin D
- Khan, Tahsin M
- Southall, Noel
- Walsh, Martin J
- Brimacombe, Kyle R
- Lunt, Sophia Y
- Johnson, Zachary R
- Yen, Katharine E
- Kunii, Kaiko
- Davidson, Shawn M
- Christofk, Heather R
- Austin, Christopher P
- Inglese, James
- Harris, Marian H
- Asara, John M
- Stephanopoulos, Gregory
- Salituro, Francesco G
- Dang, Lenny
- Auld, Douglas S
- Park, Hee-Won
- Cantley, Lewis C
- Thomas, Craig J
- Venue
- Nature Chemical Biology
- Published
- 2012-08-26
- Volume
- 8
- Issue
- 10
- Pages
- 839-847
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC3711671
- OpenAlex
- W2125836344
- Cited by
- 816
- References
- 46
- Citations by year
- 2026: 39 · 2025: 76 · 2024: 61 · 2023: 66 · 2022: 59 · 2021: 73 · 2020: 69 · 2019: 47 · 2018: 60 · 2017: 49 · 2016: 53 · 2015: 55 · 2014: 55 · 2013: 45 · 2012: 9
- FWCI
- 17.46
- Type
- journal article
- Language
- en
- Update notices
- erratum (2012-11-26)
- Open access
- green
- europepmc.org
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- University of Chicago
- Genome Canada
- Wellcome Trust
- Knut och Alice Wallenbergs Stiftelse
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Mental Health (R03MH085679)
- National Cancer Institute (5P30CA1405141, R01CA160458, P01CA120964, P30CA006516)
- National Institute of General Medical Sciences (R01 GM56203, R01GM056203)
- Biological and Environmental Research
- Argonne National Laboratory
- 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 › Biochemical and Molecular Research
- Keywords
- PKM2, tetramerization, fructose-1,6-bisphosphate, small molecule activators, PKM1, tumor growth inhibition, tumor xenografts, cancer metabolism, glucose metabolism, tyrosine phosphorylation, anabolic metabolism, enzyme activation
- MeSH terms
- Animals, Biopolymers, Cell Transformation, Neoplastic, Humans, Neoplasms, Pyruvate Kinase, Blotting, Western, Enzyme Activators, Cell Proliferation, Mice
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