Biology Reference
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The LKB1 (STK11) Suppressor
Gene
The LKB1 gene (STK11) located at chromosome 19p13.3 has been focused upon
vigorously in recent years and some have described it to be a novel suppressor gene.
It was identified and recognised for its tumour suppressor properties many years ago.
LOH and both germ line and somatic mutations of the gene were linked with the
Peutz-Jeghers syndrome (PJS) and enhanced risk of developing cancers associated
with the syndrome. Germ line mutation of the suppressor gene PTEN has also been
associated with PJS. The incidence of mutations of LKB1 in sporadic tumour is not
remarkable.
LKB1 is a serine/threonine kinase that is known directly to target AMPKs (AMP-
activated protein kinase). Several AMPKs have been identified of which the majority
are activated by LKB1 by phosphorylation of a conserved threonine residue in their
T-loop region (Bright et al., 2009). AMPK functions as an energy sensing device and
maintains energy balance by lipid and glucose metabolism, by integrating the gener-
ation of ATP and inhibiting cellular processes that consume ATP (Hardie et al., 2012;
Wang et al., 2012b). The rise of LKB1 to prominence has flowed from its associa-
tion with cell cycle regulation, microtubule dynamics, cell polarity and differentia-
tion. Not unexpectedly LKB1 regulates metabolic functions as well. Mutations of the
gene suppress or reduce the kinase activity.
The enzymatic activity and subcellular localisation of LKB1 requires it to form
complexes with STRAD (STE20-related kinase adaptor) and MO25 (mouse pro-
tein 25, the scaffolding calcium-binding protein also known as CAB39) (Boudeau
et al., 2004; Hawley et al., 2003) and LKB1 is constitutively activated in complex
with these proteins. Complex formation with STRAD is essential for the G1 sup-
pressor function of LKB1 (Baas et al., 2003) and polarisation of cells. Specific LOH
of STRAD has been encountered, but no somatic mutations in a small number of
gastric adenocarcinomas (De Leng et al., 2005). It would seem therefore that inac-
tivation of the gene might not be a solitary requisite in the pathogenesis of gastric
carcinomas, but its importance might be linked with activation of LKB1. This might
also partly account for the not so striking a correlation between loss of LKB1 and
tumorigenesis.
Expression of LKB1 and Tumorigenesis
Tumorigenesis is likely to arise from mutations, both germ line and somatic, of the
LKB1 gene. Genetic alterations as homozygous deletions or LOH are frequently
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