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

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

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)
118 Downloads (Pure)


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 languageEnglish
Article number190099
Pages (from-to)1-21
Number of pages21
JournalOpen Biology
Issue number7
Publication statusPublished - 10 Jul 2019


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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)
  • Immunology


Dive into the research topics of 'The strange case of AMPK and cancer: Dr Jekyll or Mr Hyde?'. Together they form a unique fingerprint.

Cite this