The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Distinct perturbation of the translatome by the antidiabetic drug metformin
Open accessAbstract
Metformin has been reported to lower cancer incidence among type II diabetics. Metformin exhibits antiproliferative and antineoplastic effects associated with inhibition of mammalian target of rapamycin complex 1 (mTORC1), but the mechanisms are poorly understood. We provide a unique genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) compared with metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors. Importantly, metformin's antiproliferative activity can be explained by selective translational suppression of mRNAs encoding cell-cycle regulators via the mTORC1/eukaryotic translation initiation factor 4E-binding protein pathway. Thus, metformin selectively inhibits translation of mRNAs encoding proteins that promote neoplastic proliferation, which should facilitate studies on metformin and related biguanides in cancer prevention and treatment.
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Cites
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
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AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer
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Direct multiplexed measurement of gene expression with color-coded probe pairs
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Self-citationThoreen, C. C., Kang, S. A., Chang, J. W., Liu, Q., Zhang, J., Gao, Y., Reichling, L. J., Sim, T., Sabatini, D. M., & Gray, N. S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900301200 · Cited by 1,803
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Cited by
Metformin improves healthspan and lifespan in mice
Martin-Montalvo, A., Mercken, E. M., Mitchell, S. J., Palacios, H. H., Mote, P. L., Scheibye-Knudsen, M., Gomes, A. P., Ward, T. M., Minor, R. K., Blouin, M.-J., et al. (2013) · Nature Communications · doi:10.1038/ncomms3192 · Cited by 1,445
Self-citationMaking new contacts: the mTOR network in metabolism and signalling crosstalk
Shimobayashi, M., & Hall, M. N. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3757 · Cited by 1,053
Morita, M., Gravel, S.-P., Chénard, V., Sikström, K., Zheng, L., Alain, T., Gandin, V., Avizonis, D., Arguello, M., Zakaria, C., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.10.001 · Cited by 842
Self-citationTargeting the translation machinery in cancer
Bhat, M., Robichaud, N., Hulea, L., Sonenberg, N., Pelletier, J., & Topisirovic, I. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4505 · Cited by 799
Self-citationmTOR coordinates protein synthesis, mitochondrial activity and proliferation
Morita, M., Gravel, S.-P., Hulea, L., Larsson, O., Pollak, M., St-Pierre, J., & Topisirovic, I. (2015) · Cell Cycle · doi:10.4161/15384101.2014.991572 · Cited by 552
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Metadata
- Authors
- Larsson, O., Morita, M., Topisirovic, I., Alain, T., Blouin, M.-J., Pollak, M., & Sonenberg, N.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2012-05-18
- Volume
- 109
- Issue
- 23
- Pages
- 8977-8982
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2071396361
- Cited by
- 205
- References
- 16
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Larsson, O., Morita, M., Topisirovic, I., Alain, T., Blouin, M.-J., Pollak, M., & Sonenberg, N. (2012). Distinct perturbation of the translatome by the antidiabetic drug metformin. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1201689109
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