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AMP-activated protein kinase and human cancer: cancer metabolism revisited

International Journal of Obesity volume 32, pages S36–S41 (2008)Cite this article

Abstract

AMP-activated protein kinase (AMPK) and its upstream kinase, LKB1, act to both monitor and restore cellular energy in response to energy depletion. Studied extensively in liver and skeletal muscle, AMPK is phosphorylated and activated by LKB1 in response to increasing AMP/ATP ratios, which occur in a variety of settings including hypoxia, nutrient starvation and redox imbalance. Interest in the roles of both AMPK and LKB1 in cancer has grown substantially, following the identification of LKB1 as the tumor suppressor gene mutated in the Peutz–Jegher familial cancer syndrome. Patients with the Peutz–Jegher syndrome harbor a single inactive LKB1 gene, and acquisition of a second inactivating lesion (loss of heterozygosity) leads to the development of the cancer in a variety of organs. Thus, the loss of AMPK activation is hypothesized to promote the development of malignancy. Conversely, pharmacological AMPK activation has recently been shown to be cytotoxic to many established human cancer cell lines in vitro and in human cancer xenograft and mouse cancer allografts. Previously, changes in cell metabolism that accompanied the malignant phenotype have largely been considered a consequence of cellular transformation. Now, AMPK and energy metabolism are linked to the development and maintenance of the malignant phenotype. These findings have led to renewed interest in AMPK and cancer cell metabolism in general as potential targets for cancer therapy.

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Authors and Affiliations

  1. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    F P Kuhajda

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Correspondence to F P Kuhajda.

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Conflict of interest

This work was supported by NIH grants CA87850 to FPK. Funding for some of the studies described in this article was also provided by FASgen, LLC. Under a licensing agreement between FASgen and the Johns Hopkins University, FPK is entitled to a share of royalty received by the University on sales of products described in this article. FPK owns FASgen stock, which is subject to certain restrictions under University policy. The Johns University, in accordance with its conflict of interest policies, is managing the terms of this arrangement. FP Kuhajda owns stock and is a consultant for FASgen Inc. specifically in the development of fatty acid synthase technology for cancer diagnosis.

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Kuhajda, F. AMP-activated protein kinase and human cancer: cancer metabolism revisited. Int J Obes 32 (Suppl 4), S36–S41 (2008). https://doi.org/10.1038/ijo.2008.121

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