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LKB1; linking cell structure and tumor suppression

Oncogene volume 27, pages 6908–6919 (2008)Cite this article

Abstract

Germ line mutations in the LKB1 tumor suppressor gene are associated with the Peutz–Jeghers polyposis and cancer syndrome. Somatic mutations in Lkb1 are observed in sporadic pulmonary, pancreatic and biliary cancers and melanomas. The LKB1 serine–threonine kinase functionally and biochemically links control of cellular structure and energy utilization through activation of the AMPK family of kinases. Lkb1 regulates cell polarity through downstream kinases including AMPKs, MARKs and BRSKs, and nutrient utilization and cellular metabolism through the AMPK–mTOR pathway. LKB1 has been shown to affect normal chromosomal segregation, TGF-β signaling in the mesenchyme and WNT and p53 activity. Although each of the LKB1-dependent processes and downstream pathways have been individually delineated through work across a range of experimental systems, how they relate to Lkb1's role as a tumor suppressor remains to be fully explored and elucidated. The recent development of mouse cancer models harboring engineered mutations in Lkb1 have offered insights into how LKB1 may be functioning to restrain tumorigenesis and how its role as a master regulator of polarity and metabolism could contribute to its tumor suppressor function.

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Acknowledgements

We thank Reuben Shaw and Rob Screaton for critical review of this paper.

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  1. Department of Medicine, Harvard Medical School, Massachusetts General Hospital Cancer Center, Boston, MA, USA

    A F Hezel & N Bardeesy

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  1. A F Hezel
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Hezel, A., Bardeesy, N. LKB1; linking cell structure and tumor suppression. Oncogene 27, 6908–6919 (2008). https://doi.org/10.1038/onc.2008.342

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