The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Aspartate is an endogenous metabolic limitation for tumour growth
Open accessAbstract
Defining the metabolic limitations of tumour growth will help to develop cancer therapies1. Cancer cells proliferate slower in tumours than in standard culture conditions, indicating that a metabolic limitation may restrict cell proliferation in vivo. Aspartate synthesis can limit cancer cell proliferation when respiration is impaired2–4; however, whether acquiring aspartate is endogenously limiting for tumour growth is unknown. We confirm that aspartate has poor cell permeability, which prevents environmental acquisition, whereas the related amino acid asparagine is available to cells in tumours, but cancer cells lack asparaginase activity to convert asparagine to aspartate. Heterologous expression of guinea pig asparaginase 1 (gpASNase1), an enzyme that produces aspartate from asparagine5, confers the ability to use asparagine to supply intracellular aspartate to cancer cells in vivo. Tumours expressing gpASNase1 grow at a faster rate, indicating that aspartate acquisition is an endogenous metabolic limitation for the growth of some tumours. Tumours expressing gpASNase1 are also refractory to the growth suppressive effects of metformin, suggesting that metformin inhibits tumour growth by depleting aspartate. These findings suggest that therapeutic aspartate suppression could be effective to treat cancer. Garcia-Bermudez et al. and Sullivan et al. show that endogenous aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours, and that metformin depletes aspartate to limit tumour growth.
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Cites
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Self-citationFrom Krebs to clinic: glutamine metabolism to cancer therapy
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Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells
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Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells
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Self-citationMetabolic heterogeneity in human lung tumors
Hensley, C. T., Faubert, B., Yuan, Q., Lev-Cohain, N., Jin, E., Kim, J., Jiang, L., Ko, B., Skelton, R., Loudat, L., et al. (2016) · Cell · doi:10.1016/j.cell.2015.12.034 · Cited by 1,138
Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis
Wheaton, W. W., Weinberg, S. E., Hamanaka, R. B., Soberanes, S., Sullivan, L. B., Anso, E., Glasauer, A., Dufour, E., Mutlu, G. M., Budigner, G. S., et al. (2014) · eLife · doi:10.7554/elife.02242 · Cited by 1,105
Self-citationEnvironment impacts the metabolic dependencies of Ras-driven non-small cell lung cancer
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Self-citationMetabolic determinants of cancer cell sensitivity to glucose limitation and biguanides
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Cited by
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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
Increased demand for NAD(+) relative to ATP drives aerobic glycolysis
Luengo, A., Li, Z., Gui, D. Y., Sullivan, L. B., Zagorulya, M., Do, B. T., Ferreira, R., Naamati, A., Ali, A., Lewis, C. A., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2020.12.012 · Cited by 547
Self-citationAspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours
Garcia-Bermudez, J., Baudrier, L., La, K., Zhu, X. G., Fidelin, J., Sviderskiy, V. O., Papagiannakopoulos, T., Molina, H., Snuderl, M., Lewis, C. A., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0118-z · Cited by 442
Self-citationTumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy
Bertero, T., Oldham, W. M., Grasset, E. M., Bourget, I., Boulter, E., Pisano, S., Hofman, P., Bellvert, F., Meneguzzi, G., Bulavin, D. V., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.09.012 · Cited by 393
A non-canonical tricarboxylic acid cycle underlies cellular identity
Arnold, P. K., Jackson, B. T., Paras, K. I., Brunner, J. S., Hart, M. L., Newsom, O. J., Alibeckoff, S. P., Endress, J., Drill, E., Sullivan, L. B., et al. (2022) · Nature · doi:10.1038/s41586-022-04475-w · Cited by 304
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Metadata
- Authors
- Sullivan, L. B., Luengo, A., Danai, L. V., Bush, L. N., Diehl, F. F., Hosios, A. M., Lau, A. N., Elmiligy, S., Malstrom, S., Lewis, C. A., & Vander Heiden, M. G.
- Venue
- Nature Cell Biology
- Published
- 2018-06-25
- Volume
- 20
- Issue
- 7
- Pages
- 782-788
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2808976292
- Cited by
- 341
- References
- 34
- FWCI
- 10.02
- Type
- journal article
- Language
- en
- Open access
- bronze
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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