Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Dec;22(12):1617-20.
doi: 10.1038/cr.2012.108. Epub 2012 Jul 17.

LKB1-AMPK axis revisited

Filippos Kottakis  1 , Nabeel Bardeesy
Affiliations

LKB1-AMPK axis revisited

Filippos Kottakis et al. Cell Res. 2012 Dec.

Abstract

The LKB1 tumor suppressor encodes a serine-threonine kinase whose substrates control cell metabolism, polarity, and motility. LKB1 is a major mediator of the cellular response to energy stress via activation of the master regulator of energy homeostasis, AMPK. While mutational inactivation of LKB1 promotes the development of many types of epithelial cancer, a recent report in Nature by Jeon et al. demonstrates that the LKB1-AMPK pathway can also have an unexpected positive role in tumorigenesis, acting to maintain metabolic homeostasis and attenuate oxidative stress thereby supporting the survival of cancer cells.

PubMed Disclaimer

Figures

Figure 1
Figure 1
AMPK is phosphorylated and activated by LKB1 in response to an increasing cellular AMP:ATP ratio (which reflects a decrease in energy supply). AMPK in turn phosphorylates and inactivates ACC1/2, promoting a shift from fatty acid synthesis (FAS) to fatty acid oxidation (FAO). FAS depletes NADPH that is required for H2O2 detoxification. FAO, by contrast, produces metabolites that are used by the TCA cycle, resulting in increased NADPH and enhanced cell survival. This pathway may only be transiently activated in glucose-deprived cells since ATP, produced by the coupling the TCA cycle with oxidative phosphorylation (OXPHOS), will eventually inhibit AMPK. In addition to the role of the LKB1-AMPK pathway in facilitating tumor cell survival, LKB1 is a context-specific tumor suppressor, which acts to control cell polarity and restrict cell growth via mTOR inactivation and induction of other AMPK-related kinases.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer. 2009;9:563–575. - PMC - PubMed
    1. Contreras CM, Akbay EA, Gallardo TD, et al. Lkb1 inactivation is sufficient to drive endometrial cancers that are aggressive yet highly responsive to mTOR inhibitor monotherapy. Dis Model Mech. 2010;3:181–193. - PMC - PubMed
    1. Bardeesy N, Sinha M, Hezel AF, et al. Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Nature. 2002;419:162–167. - PubMed
    1. Kato K, Ogura T, Kishimoto A, et al. Critical roles of AMP-activated protein kinase in constitutive tolerance of cancer cells to nutrient deprivation and tumor formation. Oncogene. 2002;21:6082–6090. - PubMed
    1. Laderoute KR, Amin K, Calaoagan JM, et al. 5′-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments. Mol Cell Biol. 2006;26:5336–5347. - PMC - PubMed

MeSH terms