The strange case of AMPK and cancer: Dr Jekyll or Mr Hyde?

Diana Vara-Ciruelos; Fiona M. Russell; D. Grahame Hardie

doi:10.1098/rsob.190099

The strange case of AMPK and cancer: Dr Jekyll or Mr Hyde?

Diana Vara-Ciruelos, Fiona M. Russell, D. Grahame Hardie (Lead / Corresponding author)

Cell Signalling and Immunology

Research output: Contribution to journal › Article › peer-review

107 Citations (Scopus)

200 Downloads (Pure)

Abstract

The AMP-activated protein kinase (AMPK) acts as a cellular energy sensor. Once switched on by increases in cellular AMP : ATP ratios, it acts to restore energy homeostasis by switching on catabolic pathways while switching off cell growth and proliferation. The canonical AMP-dependent mechanism of activation requires the upstream kinase LKB1, which was identified genetically to be a tumour suppressor. AMPK can also be switched on by increases in intracellular Ca2+, by glucose starvation and by DNA damage via non-canonical, AMP-independent pathways. Genetic studies of the role of AMPK in mouse cancer suggest that, before disease arises, AMPK acts as a tumour suppressor that protects against cancer, with this protection being further enhanced by AMPK activators such as the biguanide phenformin. However, once cancer has occurred, AMPK switches to being a tumour promoter instead, enhancing cancer cell survival by protecting against metabolic, oxidative and genotoxic stresses. Studies of genetic changes in human cancer also suggest diverging roles for genes encoding subunit isoforms, with some being frequently amplified, while others are mutated.

Original language	English
Article number	190099
Pages (from-to)	1-21
Number of pages	21
Journal	Open Biology
Volume	9
Issue number	7
DOIs	https://doi.org/10.1098/rsob.190099
Publication status	Published - 10 Jul 2019

Keywords

AMPK
LKB1
cancer
metabolism
tumour promoters
tumour suppressors
Tumour promoters
Metabolism
Tumour suppressors
Cancer

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology
General Neuroscience
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1098/rsob.190099Licence: CC BY

Final Published VersionFinal published version, 1.18 MBLicence: CC BY

Cite this

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title = "The strange case of AMPK and cancer: Dr Jekyll or Mr Hyde?",

abstract = "The AMP-activated protein kinase (AMPK) acts as a cellular energy sensor. Once switched on by increases in cellular AMP : ATP ratios, it acts to restore energy homeostasis by switching on catabolic pathways while switching off cell growth and proliferation. The canonical AMP-dependent mechanism of activation requires the upstream kinase LKB1, which was identified genetically to be a tumour suppressor. AMPK can also be switched on by increases in intracellular Ca2+, by glucose starvation and by DNA damage via non-canonical, AMP-independent pathways. Genetic studies of the role of AMPK in mouse cancer suggest that, before disease arises, AMPK acts as a tumour suppressor that protects against cancer, with this protection being further enhanced by AMPK activators such as the biguanide phenformin. However, once cancer has occurred, AMPK switches to being a tumour promoter instead, enhancing cancer cell survival by protecting against metabolic, oxidative and genotoxic stresses. Studies of genetic changes in human cancer also suggest diverging roles for genes encoding subunit isoforms, with some being frequently amplified, while others are mutated.",

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The strange case of AMPK and cancer: Dr Jekyll or Mr Hyde?

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Role of AMPK in Nutrient Sensing and in Cancer (Investigator Award Renewal)

Rab Detection Initiative (Joint with Stanford School of Medicine, Max Plank Institute, Neuroscience Research Australia and Parkinsons Institute California)

Cite this

The strange case of AMPK and cancer: Dr Jekyll or Mr Hyde?

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

Role of AMPK in Nutrient Sensing and in Cancer (Investigator Award Renewal)

Rab Detection Initiative (Joint with Stanford School of Medicine, Max Plank Institute, Neuroscience Research Australia and Parkinsons Institute California)

Cite this