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LKB1 and AMPK and the cancer-metabolism link - ten years after

D Grahame Hardie1* and Dario R Alessi2

Author affiliations

1 Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK

2 MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK

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Citation and License

BMC Biology 2013, 11:36  doi:10.1186/1741-7007-11-36

Published: 15 April 2013

Abstract

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.