The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability
Open accessAbstract
SUMMARY The mechanistic target of rapamycin complex 1 (mTORC1) supports proliferation through parallel induction of key anabolic processes, including protein, lipid, and nucleotide synthesis. We hypothesized that these processes are coupled to maintain anabolic balance in cells with mTORC1 activation, a common event in human cancers. Loss of the tuberous sclerosis complex (TSC) tumor suppressors results in activation of mTORC1 and development of the tumor syndrome TSC. We find that pharmacological inhibitors of guanylate nucleotide synthesis have selective deleterious effects on TSC-deficient cells, including in mouse tumor models. This effect stems from replication stress and DNA damage caused by mTORC1-driven ribosomal RNA synthesis, which renders nucleotide pools limiting. These findings reveal a metabolic vulnerability downstream of mTORC1 triggered by anabolic imbalance.
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Cites
Causes and consequences of replication stress
Zeman, M. K., & Cimprich, K. A. (2014) · Nature Cell Biology · doi:10.1038/ncb2897 · Cited by 2,079
Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism
Ying, H., Kimmelman, A. C., Lyssiotis, C. A., Hua, S., Chu, G. C., Fletcher-Sananikone, E., Locasale, J. W., Son, J., Zhang, H., Coloff, J. L., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.058 · Cited by 2,043
Self-citationActivation of a metabolic gene regulatory network downstream of mTOR complex 1
Düvel, K., Yecies, J. L., Menon, S., Raman, P., Lipovsky, A. I., Souza, A. L., Triantafellow, E., Ma, Q., Gorski, R., Cleaver, S., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.022 · Cited by 2,020
Self-citationRegulation of mammalian nucleotide metabolism and biosynthesis
Lane, A. N., & Fan, T. W.-M. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv047 · Cited by 959
mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle
Ben-Sahra, I., Hoxhaj, G., Ricoult, S. J. H., Asara, J. M., & Manning, B. D. (2016) · Science · doi:10.1126/science.aad0489 · Cited by 795
Self-citationMayer, C., & Grummt, I. (2006) · Oncogene · doi:10.1038/sj.onc.1209883 · Cited by 568
Coordinated regulation of protein synthesis and degradation by mTORC1
Zhang, Y., Nicholatos, J., Dreier, J. R., Ricoult, S. J. H., Widenmaier, S. B., Hotamisligil, G. S., Kwiatkowski, D. J., & Manning, B. D. (2014) · Nature · doi:10.1038/nature13492 · Cited by 350
Self-citationGlobal Regulation of Nucleotide Biosynthetic Genes by c-Myc
Liu, Y.-C., Li, F., Handler, J., Huang, C. R. L., Xiang, Y., Neretti, N., Sedivy, J. M., Zeller, K. I., & Dang, C. V. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002722 · Cited by 317
Cunningham, J. T., Moreno, M. V., Lodi, A., Ronen, S. M., & Ruggero, D. (2014) · Cell · doi:10.1016/j.cell.2014.03.052 · Cited by 260
Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells
Mannava, S., Grachtchouk, V., Wheeler, L. J., Im, M., Zhuang, D., Slavina, E. G., Mathews, C. K., Shewach, D. S., & Nikiforov, M. A. (2008) · Cell Cycle · doi:10.4161/cc.6390 · Cited by 257 · cited 1×
“IMPDH1 and 2 are transcriptional targets of the oncogene Myc, are upregulated in certain cancers, and have been suggested as potential targets in cells with Myc activation (Barfeld et al., 2015; Fellenberg et al., 2010; He et al., 2009; Liu et al., 2008; Mannava et al., 2008; Zou et al., 2015).”
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Cited by
Metabolic reprogramming and cancer progression
Faubert, B., Solmonson, A., & DeBerardinis, R. J. (2020) · Science · doi:10.1126/science.aaw5473 · Cited by 2,740
mTOR at the nexus of nutrition, growth, ageing and disease
Liu, G. Y., & Sabatini, D. M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0199-y · Cited by 2,737
The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism
Hoxhaj, G., & Manning, B. D. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0216-7 · Cited by 2,137
Self-citationmTOR signalling and cellular metabolism are mutual determinants in cancer
Mossmann, D., Park, S., & Hall, M. N. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0074-8 · Cited by 1,088
Macropinocytosis confers resistance to therapies targeting cancer anabolism
Jayashankar, V., & Edinger, A. L. (2020) · Nature Communications · doi:10.1038/s41467-020-14928-3 · Cited by 200
Metadata
- Authors
- Valvezan, A. J., Turner, M., Belaid, A., Lam, H. C., Miller, S. K., McNamara, M. C., Baglini, C., Housden, B. E., Perrimon, N., Kwiatkowski, D. J., Asara, J. M., Henske, E. P., & Manning, B. D.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 32
- Issue
- 5
- Pages
- 624-638.e5
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2765597781
- Cited by
- 159
- References
- 12
- FWCI
- 5.24
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Valvezan, A. J., Turner, M., Belaid, A., Lam, H. C., Miller, S. K., McNamara, M. C., Baglini, C., Housden, B. E., Perrimon, N., Kwiatkowski, D. J., Asara, J. M., Henske, E. P., & Manning, B. D. (2017). mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability. Cancer Cell. https://doi.org/10.1016/j.ccell.2017.09.013
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
