Unravelling the connection between metabolism and tumorigenesis through studies of the liver kinase B1 tumour suppressor

• Main Author: David B Shackelford
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2013-01-01
• Series: Journal of Carcinogenesis
• Subjects: AMP-activated protein kinase; fluoro-deoxyglucose positron emission tomography; liver kinase B1; mammalian target of rapamycin complex 1; therapeutics; Warburg
• Online Access: http://www.carcinogenesis.com/article.asp?issn=1477-3163;year=2013;volume=12;issue=1;spage=16;epage=16;aulast=Shackelford

The liver kinase B1 (LKB1) tumour suppressor functions as a master regulator of growth, metabolism and survival in cells, which is frequently mutated in sporadic human non-small cell lung and cervical cancers. LKB1 functions as a key upstream activator of the AMP-activated protein kinase (AMPK), a central metabolic switch found in all eukaryotes that govern glucose and lipid metabolism and autophagy in response to alterations in nutrients and intracellular energy levels. The LKB1/AMPK signalling pathway suppresses mammalian target of rapamycin complex 1 (mTORC1), an essential regulator of cell growth in all eukaryotes that is deregulated in a majority of human cancers. LKB1 inactivation in cancer leads to both tumorigenesis and metabolic deregulation through the AMPK and mTORC1-signalling axis and there remain critical challenges to elucidate the direct role LKB1 inactivation plays in driving aberrant metabolism and tumour growth. This review addresses past and current efforts to delineate the molecular mechanisms fueling metabolic deregulation and tumorigenesis following LKB1 inactivation as well as translational promise of therapeutic strategies aimed at targeting LKB1-deficient tumors.