The DOI matches its Crossref record; 91 of the 91 references it cites were found in a registry or an index.
LKB1 and AMPK and the cancer-metabolism link - ten years after
Open accessAbstract
The identification of a complex containing the tumor suppressor LKB1 as the critical upstream kinase required for the activation of AMP-activated protein kinase (AMPK) by metabolic stress was reported in an article in Journal of Biology in 2003. This finding represented the first clear link between AMPK and cancer. Here we briefly discuss how this discovery came about, and describe some of the insights, especially into the role of AMPK in cancer, that have followed from it. In September 2003, our groups published a joint paper [ 1 ] in Journal of Biology (now BMC Biology ) that identified the long-sought and elusive upstream kinase acting on AMP-activated protein kinase (AMPK) as a complex containing LKB1, a known tumor suppressor. Similar findings were reported at about the same time by David Carling and Marian Carlson [ 2 ] and by Reuben Shaw and Lew Cantley [ 3 ]; at the time of writing these three papers have received between them a total of over 2,000 citations. These findings provided a direct link between a protein kinase, AMPK, which at the time was mainly associated with regulation of metabolism, and another protein kinase, LKB1, which was known from genetic studies to be a tumor suppressor. While the idea that cancer is in part a metabolic disorder (first suggested by Warburg in the 1920s [ 4 ]) is well recognized today [ 5 ], this was not the case in 2003, and our paper perhaps contributed towards its renaissance. The aim of this short review is to recall how we made the original finding, and to discuss some of the directions that these findings have taken the field in the ensuing ten years.
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Cites
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y.-J., Jiang, Q., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,304
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
The protein kinase complement of the human genome
Manning, G., Whyte, D. B., Martinez, R., Hunter, T., & Sudarsanam, S. (2002) · Science · doi:10.1126/science.1075762 · Cited by 8,145
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602
Self-citationTSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914
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
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AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
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Cited by
The interplay between cell signalling and the mevalonate pathway in cancer
Mullen, P. J., Yu, R., Longo, J., Archer, M. C., & Penn, L. Z. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.76 · Cited by 699
Degradation of AMPK by a Cancer-Specific Ubiquitin Ligase
Pineda, C. T., Ramanathan, S., Fon Tacer, K., Weon, J. L., Potts, M. B., Ou, Y.-H., White, M. A., & Potts, P. R. (2015) · Cell · doi:10.1016/j.cell.2015.01.034 · Cited by 389
Petherick, K. J., Conway, O. J. L., Mpamhanga, C., Osborne, S. A., Kamal, A., Saxty, B., & Ganley, I. G. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.c114.627778 · Cited by 366
MYC and metabolism on the path to cancer
Hsieh, A. L., Walton, Z. E., Altman, B. J., Stine, Z. E., & Dang, C. V. (2015) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2015.08.003 · Cited by 332
Loss of the Tumor Suppressor LKB1 Promotes Metabolic Reprogramming of Cancer Cells via HIF-1α
Faubert, B., Vincent, E. E., Griss, T., Samborska, B., Izreig, S., Svensson, R. U., Mamer, O. A., Avizonis, D., Shackelford, D. B., Shaw, R. J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1312570111 · Cited by 278
Metadata
- Authors
- Hardie, D. G., & Alessi, D. R.
- Venue
- BMC Biology
- Published
- 2013-04-15
- Volume
- 11
- Issue
- 1
- Pages
- 36-36
- ISSN
- 1741-7007 (ISSN-L)
- OpenAlex
- W2079551052
- Cited by
- 301
- References
- 91
- FWCI
- 16.94
- Type
- journal article
- Language
- en
- Open access
- gold
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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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