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PMID: 16613876 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

AMPK and cell proliferation--AMPK as a therapeutic target for atherosclerosis and cancer.

The Journal of physiology ·Vol. 574 ·No. Pt 1 ·2006-07-01 ·Pages 63-71

Motoshima H, Goldstein BJ, Igata M, Araki E

Abstract

AMPK is a serine/threonine protein kinase, which serves as an energy sensor in all eukaryotic cell types. Published studies indicate that AMPK activation strongly suppresses cell proliferation in non-malignant cells as well as in tumour cells. These actions of AMPK appear to be mediated through multiple mechanisms including regulation of the cell cycle and inhibition of protein synthesis, de novo fatty acid synthesis, specifically the generation of mevalonate as well as other products downstream of mevalonate in the cholesterol synthesis pathway. Cell cycle regulation by AMPK is mediated by up-regulation of the p53-p21 axis as well as regulation of TSC2-mTOR (mammalian target of rapamycin) pathway. The AMPK signalling network contains a number of tumour suppressor genes including LKB1, p53, TSC1 and TSC2, and overcomes growth factor signalling from a variety of stimuli (via growth factors and by abnormal regulation of cellular proto-oncogenes including PI3K, Akt and ERK). These observations suggest that AMPK activation is a logical therapeutic target for diseases rooted in cellular proliferation, including atherosclerosis and cancer. In this review, we discuss about exciting recent advances indicating that AMPK functions as a suppressor of cell proliferation by controlling a variety of cellular events in normal cells as well as in tumour cells.

MeSH Terms
AMP-Activated Protein Kinases Antineoplastic Agents/administration & dosage Atherosclerosis/drug therapy,enzymology Cardiotonic Agents/administration & dosage Cell Proliferation/drug effects Drug Delivery Systems/methods Humans Male Multienzyme Complexes/drug effects,metabolism Neoplasms/drug therapy,enzymology Protein Serine-Threonine Kinases/drug effects,metabolism
Chemicals
Antineoplastic Agents Cardiotonic Agents Multienzyme Complexes Protein Serine-Threonine Kinases AMP-Activated Protein Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Motoshima Hiroyuki
Department of Metabolic Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 8554, Japan. hmoto@gpo.kumamoto-u.ac.jp
Goldstein Barry J
Igata Motoyuki
Araki Eiichi
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1113/jphysiol.2006.108324
Email
hmoto@gpo.kumamoto-u.ac.jp
Published
2006-07-01
Epub
2006-00-13
Pages
63-71
Language
English
Region
England
NLM ID
0266262
PMCID
PMC1817805
Subset
IM
Grants
NIDDK NIH HHS · R01 DK063018 · United States
NIDDK NIH HHS · R01 DK071360 · United States
NIDDK NIH HHS · DK63018 · United States
NIDDK NIH HHS · DK71360 · United States
External Links
PubMed source DOI: 10.1113/jphysiol.2006.108324 PMC Full Text View journal details
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