AMP-Activated Protein Kinase: Friend or Foe in Cancer?

Vara-Ciruelos, Diana; Dandapani, Madhumita; Hardie, D. Grahame

Abstract

The AMP-activated protein kinase (AMPK) is activated by energy stress and restores homeostasis by switching on catabolism, while switching off cell growth and proliferation. Findings that AMPK acts downstream of the tumor suppressor LKB1 have suggested that AMPK might also suppress tu-morigenesis. In mouse models of B and T cell lymphoma in which genetic loss of AMPK occurred before tumor initiation, tumorigenesis was accelerated , confirming that AMPK has tumor-suppressor functions. However, when loss of AMPK in a T cell lymphoma model occurred after tumor initiation , or simultaneously with tumor initiation in a lung cancer model, the disease was ameliorated. Thus, once tumorigenesis has occurred, AMPK switches from tumor suppression to tumor promotion. Analysis of alterations in AMPK genes in human cancers suggests similar dichotomies, with some genes being frequently amplified while others are mutated. Overall, while AMPK-activating drugs might be effective in preventing cancer, in some cases AMPK inhibitors might be required to treat it.

Citation

Vara-Ciruelos, D., Dandapani, M., & Hardie, D. G. (2020). AMP-Activated Protein Kinase: Friend or Foe in Cancer?. Annual Review of Cancer Biology, 4(1), 1-16. https://doi.org/10.1146/annurev-cancerbio-030419-033619

• Journal Article Type: Article
• Acceptance Date: Oct 22, 2019
• Online Publication Date: Nov 6, 2019
• Publication Date: Mar 4, 2020
• Deposit Date: Nov 15, 2019
• Publicly Available Date: Jul 30, 2020
• Journal: Annual Review of Cancer Biology
• Print ISSN: 2472-3428
• Electronic ISSN: 2472-3428
• Publisher: Annual Reviews
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 1
• Pages: 1-16
• DOI: https://doi.org/10.1146/annurev-cancerbio-030419-033619
• Public URL: https://nottingham-repository.worktribe.com/output/3234121
• Publisher URL: https://www.annualreviews.org/doi/10.1146/annurev-cancerbio-030419-033619
• Additional Information: This journal has a subscribe to open policy- I am not sure if this makes it open access. to be on the safe side, I have said no to this in the box.