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

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    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.

    Original languageEnglish
    Article number36
    Pages (from-to)1-11
    Number of pages11
    JournalBMC Biology
    Volume11
    DOIs
    Publication statusPublished - 15 Apr 2013

    Keywords

    • DIABETIC-PATIENTS
    • PEUTZ-JEGHERS-SYNDROME
    • LKB1-AMPK PATHWAY
    • TUMOR-SUPPRESSOR LKB1
    • ACTIVATED PROTEIN-KINASE
    • ACETYL-COA CARBOXYLASE
    • YEAST SNF1
    • GLUCOSE-UPTAKE
    • UPSTREAM KINASES
    • CELLULAR-ENERGY

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