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Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides
Open accessAbstract
As the concentrations of highly consumed nutrients, particularly glucose, are generally lower in tumours than in normal tissues, cancer cells must adapt their metabolism to the tumour microenvironment. A better understanding of these adaptations might reveal cancer cell liabilities that can be exploited for therapeutic benefit. Here we developed a continuous-flow culture apparatus (Nutrostat) for maintaining proliferating cells in low-nutrient media for long periods of time, and used it to undertake competitive proliferation assays on a pooled collection of barcoded cancer cell lines cultured in low-glucose conditions. Sensitivity to low glucose varies amongst cell lines, and an RNA interference (RNAi) screen pinpointed mitochondrial oxidative phosphorylation (OXPHOS) as the major pathway required for optimal proliferation in low glucose. We found that cell lines most sensitive to low glucose are defective in the OXPHOS upregulation that is normally caused by glucose limitation as a result of either mitochondrial DNA (mtDNA) mutations in complex I genes or impaired glucose utilization. These defects predict sensitivity to biguanides, antidiabetic drugs that inhibit OXPHOS, when cancer cells are grown in low glucose or as tumour xenografts. Notably, the biguanide sensitivity of cancer cells with mtDNA mutations was reversed by ectopic expression of yeast NDI1, a ubiquinone oxidoreductase that allows bypass of complex I function. Thus, we conclude that mtDNA mutations and impaired glucose utilization are potential biomarkers for identifying tumours with increased sensitivity to OXPHOS inhibitors.
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“These findings confirm previous studies that analyzed inhibition of either glycolysis or OXPHOS, and observed an increase in the activity of the other pathway (Hao et al., 2010; Jose et al., 2011; Birsoy et al., 2014; Dykens et al., 2008).”
From Combination of Hypoglycemia and Metformin Impairs Tumor Metabolic Plasticity and Growth by Modulating the PP2A-GSK3β-MCL-1 Axis (2019) · cites this paper as Birsoy et al., 2014
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“Cancer cells with reduced OXPHOS due to either mutated mitochondrial DNA or impaired glucose utilization were unable to initiate this adaptive response, and were thus particularly sensitive to glucose deprivation to one-tenth of normal levels (Birsoy et al., 2014).”
From Combination of Hypoglycemia and Metformin Impairs Tumor Metabolic Plasticity and Growth by Modulating the PP2A-GSK3β-MCL-1 Axis (2019) · cites this paper as Birsoy et al., 2014
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“These results are consistent with previous studies reporting the synergism of the metformin/low glucose combination (Birsoy et al., 2014; Zhuang et al., 2014).”
From Combination of Hypoglycemia and Metformin Impairs Tumor Metabolic Plasticity and Growth by Modulating the PP2A-GSK3β-MCL-1 Axis (2019) · cites this paper as Birsoy et al., 2014
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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
Metformin and reduced risk of cancer in diabetic patients
Evans, J. M. M., Donnelly, L. A., Emslie-Smith, A. M., Alessi, D. R., & Morris, A. D. (2005) · BMJ · doi:10.1136/bmj.38415.708634.f7 · Cited by 2,388
OWEN, M. R., DORAN, E., & HALESTRAP, A. P. (2000) · Biochemical Journal · doi:10.1042/bj3480607 · Cited by 2,157
Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
Possemato, R., Marks, K. M., Shaul, Y. D., Pacold, M. E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.-K., Jang, H. G., Jha, A. K., et al. (2011) · Nature · doi:10.1038/nature10350 · Cited by 1,683
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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
Self-citationEl-Mir, M.-Y., Nogueira, V., Fontaine, E., Avéret, N., Rigoulet, M., & Leverve, X. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.1.223 · Cited by 1,399
Hirayama, A., Kami, K., Sugimoto, M., Sugawara, M., Toki, N., Onozuka, H., Kinoshitá, T., Saito, N., Ochiai, A., Tomita, M., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4806 · Cited by 965
Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis
DeCensi, A., Puntoni, M., Goodwin, P., Cazzaniga, M., Gennari, A., Bonanni, B., & Gandini, S. (2010) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-10-0157 · Cited by 918
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Crabtree, H. G. (1929) · Biochemical Journal · doi:10.1042/bj0230536 · Cited by 864
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Self-citationCantor, J. R., Abu-Remaileh, M., Kanarek, N., Freinkman, E., Gao, X., Louissaint, A., Lewis, C. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.03.023 · Cited by 638
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Self-citationFacilitative glucose transporters: Implications for cancer detection, prognosis and treatment
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Sleire, L., Førde, H. E., Netland, I. A., Leiss, L., Skeie, B. S., & Enger, P. Ø. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.07.013 · Cited by 329
Balsa, E., Soustek, M. S., Thomas, A. J., Cogliati, S., García‐Poyatos, C., Martín-García, E., Jedrychowski, M. P., Gygi, S. P., Enrı́quez, J. A., & Puigserver, P. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.03.031 · Cited by 322
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Elgendy, M., Cirò, M., Hosseini, A., Weiszmann, J., Mazzarella, L., Ferrari, E., Cazzoli, R., Curigliano, G., DeCensi, A., Bonanni, B., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.03.007 · Cited by 299
Repurposing metformin for the prevention of cancer and cancer recurrence
Heckman‐Stoddard, B. M., DeCensi, A., Sahasrabuddhe, V. V., & Ford, L. G. (2017) · Diabetologia · doi:10.1007/s00125-017-4372-6 · Cited by 302
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Metabolic Plasticity as a Determinant of Tumor Growth and Metastasis
Lehuédé, C., Dupuy, F., Rabinovitch, R., Jones, R. G., & Siegel, P. M. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0266 · Cited by 288
Repurposing metformin: an old drug with new tricks in its binding pockets
Pryor, R., & Cabreiro, F. (2015) · Biochemical Journal · doi:10.1042/bj20150497 · Cited by 280
Vincent, E. E., Sergushichev, A., Griss, T., Gingras, M., Samborska, B., Ntimbane, T., Coelho, P. P., Blagih, J., Raissi, T. C., Choinière, L., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.08.013 · Cited by 281
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Bonekamp, N. A., Peter, B., Hillen, H. S., Felser, A., Bergbrede, T., Choidas, A., Horn, M., Unger, A., Lucrezia, R. D., Atanassov, I., et al. (2020) · Nature · doi:10.1038/s41586-020-03048-z · Cited by 269
Saito, Y., Chapple, R. H., Lin, A. J., Kitano, A., & Nakada, D. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.08.019 · Cited by 279
Chourasia, A. H., Boland, M. L., & Macleod, K. F. (2015) · Cancer & Metabolism · doi:10.1186/s40170-015-0130-8 · Cited by 284
Gopal, R. K., Kübler, K., Calvo, S. E., Polak, P. P., Livitz, D. G., Rosebrock, D., Sadow, P. M., Campbell, B., Donovan, S. E., Amin, S., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.06.013 · Cited by 271
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Soukas, A. A., Hao, H., & Wu, L. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.07.015 · Cited by 266
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Gaude, E., & Frezza, C. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-10 · Cited by 266
Cárdenas, C., Müller, M., McNeal, A. S., Lovy, A., Jaña, F., Bustos, G., Urra, F. A., Smith‐Cortinez, N., Molgó, J., Diehl, J. A., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.02.030 · Cited by 250
Villani, L. A., Smith, B. K., Marcinko, K., Ford, R. J., Broadfield, L. A., Green, A. E., Houde, V. P., Muti, P. C., Tsakiridis, T. K., & Steinberg, G. R. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.08.014 · Cited by 247
Metformin Targets Central Carbon Metabolism and Reveals Mitochondrial Requirements in Human Cancers
Liu, X., Romero, I. L., Litchfield, L. M., Lengyel, E. R., & Locasale, J. W. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.005 · Cited by 229
Kalyanaraman, B., Cheng, G., Hardy, M., Ouari, O., López, M., Joseph, J., Zielonka, J., & Dwinell, M. B. (2017) · Redox Biology · doi:10.1016/j.redox.2017.09.020 · Cited by 239
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Fu, X., Chin, R., Vergnes, L., Hwang, H., Deng, G., Xing, Y., Pai, M. Y., Li, S., Ta, L. H., Fazlollahi, F., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.009 · Cited by 230
Han, H., Hou, Y., Chen, X., Zhang, P., Kang, M., Jin, Q., Ji, J., & Gao, M. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c00650 · Cited by 233
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Counihan, J. L., Grossman, E. A., & Nomura, D. K. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00775 · Cited by 236
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Lu, J. (2019) · Cancer and Metastasis Reviews · doi:10.1007/s10555-019-09794-5 · Cited by 221
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Danhier, P., Bański, P., Payen, V. L., Grasso, D., Ippolito, L., Sonveaux, P., & Porporato, P. E. (2017) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2017.02.001 · Cited by 230
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Momcilovic, M., Jones, A., Bailey, S. T., Waldmann, C. M., Li, R., Lee, J. T., Abdelhady, G., Gomez, A., Holloway, T., Schmid, E., et al. (2019) · Nature · doi:10.1038/s41586-019-1715-0 · Cited by 214
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Griss, T., Vincent, E. E., Egnatchik, R. A., Chen, J., Ma, E. H., Faubert, B., Viollet, B., DeBerardinis, R. J., & Jones, R. G. (2015) · PLoS Biology · doi:10.1371/journal.pbio.1002309 · Cited by 216
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Martinez‐Outschoorn, U., Sotgia, F., & Lisanti, M. P. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3915 · Cited by 216
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Minton, D. R., Nam, M., McLaughlin, D. J., Shin, J., Bayraktar, E. C., Alvarez, S., Sviderskiy, V. O., Papagiannakopoulos, T. Y., Sabatini, D. M., Birsoy, K., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.01.024 · Cited by 192
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Woller, N., Gürlevik, E., Fleischmann-Mundt, B., Schumacher, A., Knocke, S., Kloos, A., Saborowski, M., Geffers, R., Manns, M. P., Wirth, T. C., et al. (2015) · Molecular Therapy · doi:10.1038/mt.2015.115 · Cited by 189
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Mayers, J. R., & Heiden, M. G. V. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.01.004 · Cited by 190
Molenaar, R. J., Radivoyevitch, T., Maciejewski, J. P., Noorden, C. J. F. V., & Bleeker, F. E. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.05.004 · Cited by 186
He, T., Xu, H., Zhang, Y., Yi, S., Cui, R., Xing, S., Wei, C., Lin, J., & Huang, P. (2020) · Theranostics · doi:10.7150/thno.40439 · Cited by 177
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Thakur, C., & Chen, F. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.06.006 · Cited by 176
Reni, M., Dugnani, E., Cereda, S., Belli, C., Balzano, G., Nicoletti, R., Liberati, D., Pasquale, V., Scavini, M., Maggiora, P. M., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1722 · Cited by 174
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Pouysségur, J., Marchiq, I., Parks, S. K., Durivault, J., Ždralević, M., & Vučetić, M. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.07.004 · Cited by 178
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LeBoeuf, S. E., Wu, W. L., Karakousi, T. R., Karadal, B., Jackson, S. R., Davidson, S. M., Wong, K.-K., Koralov, S. B., Sayin, V. I., & Papagiannakopoulos, T. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.012 · Cited by 150
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Momcilovic, M., Bailey, S. T., Lee, J. T., Fishbein, M. C., Magyar, C., Braas, D., Graeber, T., Jackson, N. J., Czernin, J., Emberley, E., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.061 · Cited by 157
Thakur, S., Daley, B., Gaskins, K., Vasko, V. V., Boufraqech, M., Patel, D., Sourbier, C., Reece, J. M., Cheng, S.-Y., Kebebew, E., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3167 · Cited by 157
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Liu, S., Fu, S., Wang, G., Cao, Y., Li, L., Li, X., Yang, J. J., Li, N., Shan, Y., Cao, Y., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.06.013 · Cited by 159
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Nagel, R., Semenova, E. A., & Berns, A. J. M. (2016) · EMBO Reports · doi:10.15252/embr.201643030 · Cited by 161
Pei, C., Liu, C., Wang, Y., Cheng, D., Li, R., Shu, W., Zhang, C., Hu, W., Jin, A., Yang, Y., et al. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202001135 · Cited by 152
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 152
Li, J., Huang, Q., Long, X.-Q., Guo, X., Sun, X., Jin, X., Li, Z., Ren, T., Yuan, P., Huang, X., et al. (2017) · Oncogene · doi:10.1038/onc.2017.98 · Cited by 151
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Nagarajan, A. G., Dogra, S. K., Sun, L., Gandotra, N., Ho, T., Cai, G., Cline, G. W., Kumar, P., Cowles, R. A., & Wajapeyee, N. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.07.014 · Cited by 145
Metadata
- Authors
- Birsoy, K., Possemato, R., Lorbeer, F. K., Bayraktar, E. C., Thiru, P., Yucel, B., Wang, T., Chen, W. W., Clish, C. B., & Sabatini, D. M.
- Affiliations
- Broad Institute (US)
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Sabatini, David M.
- ORCID
- Venue
- Nature
- Published
- 2014-03-16
- Volume
- 508
- Issue
- 7494
- Pages
- 108-112
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4012432
- OpenAlex
- W2104696999
- Cited by
- 710
- References
- 27
- Citations by year
- 2026: 17 · 2025: 44 · 2024: 58 · 2023: 46 · 2022: 60 · 2021: 75 · 2020: 83 · 2019: 71 · 2018: 51 · 2017: 49 · 2016: 61 · 2015: 59 · 2014: 35
- FWCI
- 21.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (CA129105, K99CA168940, CA103866, R01CA103866, R01CA129105, R00CA168940)
- National Institute of General Medical Sciences (T32GM007287)
- National Institute of Allergy and Infectious Diseases (AI-07389, T32AI007389)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- 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 › PI3K/AKT/mTOR signaling in cancer
- Keywords
- glucose limitation, biguanides, mitochondrial oxidative phosphorylation, cancer metabolism, mitochondrial DNA mutations, complex I, antidiabetic drugs, OXPHOS inhibitors, continuous flow culture, tumor microenvironment, NDI1, glucose utilization, cancer cell lines, drug sensitivity biomarkers
- MeSH terms
- Adenosine Triphosphate, Animals, Biguanides, Culture Media, DNA, Mitochondrial, Glucose, Humans, Hypoglycemic Agents, Male, Mitochondria, Mutation, Neoplasm Transplantation, Neoplasms, Oxidative Phosphorylation, Phenformin, Cell Culture Techniques, Xenograft Model Antitumor Assays, Saccharomyces cerevisiae Proteins, RNA Interference, Electron Transport Complex I, Cell Line, Tumor, Cell Proliferation, Mice, Molecular Typing
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