The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
PKM2 Isoform-Specific Deletion Reveals a Differential Requirement for Pyruvate Kinase in Tumor Cells
Open accessAbstract
The pyruvate kinase M2 isoform (PKM2) is expressed in cancer and plays a role in regulating anabolic metabolism. To determine whether PKM2 is required for tumor formation or growth, we generated mice with a conditional allele that abolishes PKM2 expression without disrupting PKM1 expression. PKM2 deletion accelerated mammary tumor formation in a Brca1-loss-driven model of breast cancer. PKM2 null tumors displayed heterogeneous PKM1 expression, with PKM1 found in nonproliferating tumor cells and no detectable pyruvate kinase expression in proliferating cells. This suggests that PKM2 is not necessary for tumor cell proliferation and implies that the inactive state of PKM2 is associated with the proliferating cell population within tumors, whereas nonproliferating tumor cells require active pyruvate kinase. Consistent with these findings, variable PKM2 expression and heterozygous PKM2 mutations are found in human tumors. These data suggest that regulation of PKM2 activity supports the different metabolic requirements of proliferating and nonproliferating tumor cells.
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“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 active study”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Israelsen et al., 2013
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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-citationRegulation 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
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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
Self-citationMacropinocytosis of protein is an amino acid supply route in Ras-transformed cells
Commisso, C., Davidson, S. M., Soydaner-Azeloglu, R. G., Parker, S. J., Kamphorst, J. J., Hackett, S., Grabocka, E., Nofal, M., Drebin, J. A., Thompson, C. B., et al. (2013) · Nature · doi:10.1038/nature12138 · Cited by 1,683
Self-citationTargeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice
Sonveaux, P., Végran, F., Schroeder, T., Wergin, M., Verrax, J., Rabbani, Z. N., Saedeleer, C. J. D., Kennedy, K. M., Diepart, C., Jordan, B. F., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36843 · Cited by 1,635
Pyruvate Kinase M2 Is a PHD3-Stimulated Coactivator for Hypoxia-Inducible Factor 1
Luo, W., Hu, H., Chang, R., Zhong, J., Knabel, M., O'Meally, R., Cole, R. N., Pandey, A., & Semenza, G. L. (2011) · Cell · doi:10.1016/j.cell.2011.03.054 · Cited by 1,463
Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation
Jain, M., Nilsson, R., Sharma, S., Madhusudhan, N., Kitami, T., Souza, A. L., Kafri, R., Kirschner, M. W., Clish, C. B., & Mootha, V. K. (2012) · Science · doi:10.1126/science.1218595 · Cited by 1,403
Anastasiou, D., Poulogiannis, G., Asara, J. M., Boxer, M. B., Jiang, J., Shen, M., Bellinger, G., Sasaki, A. T., Locasale, J. W., Auld, D. S., et al. (2011) · Science · doi:10.1126/science.1211485 · Cited by 1,218
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Heiden, M. G. V., & DeBerardinis, R. J. (2017) · Cell · doi:10.1016/j.cell.2016.12.039 · Cited by 2,369
Palsson-McDermott, E. M., Curtis, A. M., Goel, G., Lauterbach, M. A. R., Sheedy, F. J., Gleeson, L. E., van den Bosch, M. W. M., Quinn, S. R., Domingo-Fernandez, R., Johnston, D. G. W., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2014.12.005 · Cited by 1,397
“BMDMs from mice carrying a PKM2fl/fl allele were previously described (Israelsen et al., 2013).”
InfluentialTargeting cancer metabolism in the era of precision oncology
Stine, Z. E., Schug, Z. T., Salvino, J. M., & Dang, C. V. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00339-6 · Cited by 1,189
Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy?
Hay, N. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.77 · Cited by 1,152
Metadata
- Authors
- 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., Burga, L. N., Xie, J., Jurczak, M. J., DePinho, R. A., Clish, C. B., Jacks, T., Kibbey, R. G., Wulf, G. M., Di Vizio, D., Mills, G. B., Cantley, L. C., & Vander Heiden, M. G.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- The University of Texas MD Anderson Cancer Center (US)
- Beth Israel Deaconess Medical Center (US)
- Dana-Farber Cancer Institute (US)
- Cell Signaling Technology (United States) (US)
- Yale University (US)
- Broad Institute (US)
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 155
- Issue
- 2
- Pages
- 397-409
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3850755
- OpenAlex
- W1975215468
- Cited by
- 549
- References
- 48
- Citations by year
- 2026: 25 · 2025: 35 · 2024: 46 · 2023: 32 · 2022: 56 · 2021: 56 · 2020: 43 · 2019: 41 · 2018: 41 · 2017: 44 · 2016: 32 · 2015: 41 · 2014: 50 · 2013: 5
- FWCI
- 14.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- Damon Runyon Cancer Research Foundation
- Richard and Susan Smith Family Foundation
- Agios Pharmaceuticals
- National Institutes of Health (DK059635)
- National Cancer Institute (5-P30-CA14051, P50CA098258, K08CA136983, R01CA168653, R00CA131472, P30CA014051, P01CA117969, P30CA147882)
- National Institute of General Medical Sciences (R01GM056203)
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK059635, R01DK092606, DK059635)
- 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, PKM1, tumor cell proliferation, mammary tumor formation, BRCA1, breast cancer, cancer metabolism, conditional knockout mice, tumor heterogeneity, anabolic metabolism
- MeSH terms
- Animals, Base Sequence, Breast Neoplasms, Exons, Female, Humans, Isoenzymes, Mammary Neoplasms, Experimental, Mice, Inbred C57BL, Models, Molecular, Molecular Sequence Data, Mutation, Neoplasm Metastasis, Neoplasm Transplantation, Pyruvate Kinase, RNA Splicing, Mutagenesis, Gene Deletion, Mice, Gene Knockout Techniques, Heterografts
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