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The LKB1–AMPK pathway: metabolism and growth control in tumour suppression

The LKB1–AMPK pathway: metabolism and growth control in tumour suppression The serine–threonine liver kinase B1 (LKB1) is inactivated in Peutz–Jeghers syndrome and a large percentage of sporadic non-small cell lung carcinomas and cervical carcinomas. LKB1 acts a master upstream kinase, directly phosphorylating and activating AMP-activated protein kinase (AMPK) and a family of 12 related kinases that have crucial roles in cell growth, metabolism and polarity. The LKB1–AMPK pathway serves as a metabolic checkpoint in the cell, arresting cell growth in conditions of low intracellular ATP levels, such as in low nutrient conditions. One of the central mitogenic pathways that is suppressed by LKB1 and AMPK signalling is the mTOR complex 1 pathway, which is inhibited through AMPK phosphorylation of tuberous sclerosis complex 2 and regulatory associated protein of mTOR (raptor). Overnutrition and hyperglycaemia can suppress LKB1–AMPK signalling, which might contribute to an increased cancer risk in patients who are obese or diabetic. Conversely, activation of LKB1–AMPK signalling might contribute to the suppression of cancer risk that is associated with exercise and caloric restriction. Will AMPK-activating drugs, including existing diabetes therapeutics, find clinical usefulness as anticancer agents? http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Reviews Cancer Springer Journals

The LKB1–AMPK pathway: metabolism and growth control in tumour suppression

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References (208)

Publisher
Springer Journals
Copyright
Copyright © 2009 by Nature Publishing Group
Subject
Biomedicine; Biomedicine, general; Cancer Research
ISSN
1474-175X
eISSN
1474-1768
DOI
10.1038/nrc2676
Publisher site
See Article on Publisher Site

Abstract

The serine–threonine liver kinase B1 (LKB1) is inactivated in Peutz–Jeghers syndrome and a large percentage of sporadic non-small cell lung carcinomas and cervical carcinomas. LKB1 acts a master upstream kinase, directly phosphorylating and activating AMP-activated protein kinase (AMPK) and a family of 12 related kinases that have crucial roles in cell growth, metabolism and polarity. The LKB1–AMPK pathway serves as a metabolic checkpoint in the cell, arresting cell growth in conditions of low intracellular ATP levels, such as in low nutrient conditions. One of the central mitogenic pathways that is suppressed by LKB1 and AMPK signalling is the mTOR complex 1 pathway, which is inhibited through AMPK phosphorylation of tuberous sclerosis complex 2 and regulatory associated protein of mTOR (raptor). Overnutrition and hyperglycaemia can suppress LKB1–AMPK signalling, which might contribute to an increased cancer risk in patients who are obese or diabetic. Conversely, activation of LKB1–AMPK signalling might contribute to the suppression of cancer risk that is associated with exercise and caloric restriction. Will AMPK-activating drugs, including existing diabetes therapeutics, find clinical usefulness as anticancer agents?

Journal

Nature Reviews Cancer – Springer Journals

Published: Aug 1, 2009

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