2. Academic Validation
  3. AMPK activation protects against prostate cancer by inducing a catabolic cellular state

AMPK activation protects against prostate cancer by inducing a catabolic cellular state

  • Cell Rep. 2023 Apr 15;42(4):112396. doi: 10.1016/j.celrep.2023.112396.
Lucy Penfold 1,  Angela Woods 2,  Alice E Pollard 3,  Julia Arizanova 2,  Eneko Pascual-Navarro 2,  Phillip J Muckett 2,  Marian H Dore 2,  Alex Montoya 2,  Chad Whilding 2,  Louise Fets 2,  Joao Mokochinski 2,  Theodora A Constantin 4,  Anabel Varela-Carver 4,  Damien A Leach 4,  Charlotte L Bevan 4,  Alexander Yu Nikitin 5,  Zoe Hall 6,  David Carling 7
Affiliations

Affiliations

  • 1 MRC London Institute of Medical Sciences, Hammersmith Hospital Campus, Imperial College London, London W12 0NN, UK. Electronic address: [email protected].
  • 2 MRC London Institute of Medical Sciences, Hammersmith Hospital Campus, Imperial College London, London W12 0NN, UK.
  • 3 Institute of Clinical Sciences, Imperial College London, London, UK.
  • 4 Imperial Centre for Translational and Experimental Medicine, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.
  • 5 Department of Biomedical Sciences and Cornell Stem Cell Program, Cornell University, Ithaca, NY, USA.
  • 6 Biomolecular Medicine, Division of Systems Medicine, Department of Metabolism, Digestion, and Reproduction, Imperial College London, London, UK.
  • 7 MRC London Institute of Medical Sciences, Hammersmith Hospital Campus, Imperial College London, London W12 0NN, UK; Institute of Clinical Sciences, Imperial College London, London, UK. Electronic address: [email protected].
PMID: 37061917 DOI: 10.1016/j.celrep.2023.112396
Abstract

Emerging evidence indicates that metabolic dysregulation drives prostate Cancer (PCa) progression and metastasis. AMP-activated protein kinase (AMPK) is a master regulator of metabolism, although its role in PCa remains unclear. Here, we show that genetic and pharmacological activation of AMPK provides a protective effect on PCa progression in vivo. We show that AMPK activation induces PGC1α expression, leading to catabolic metabolic reprogramming of PCa cells. This catabolic state is characterized by increased mitochondrial gene expression, increased fatty acid oxidation, decreased lipogenic potential, decreased cell proliferation, and decreased cell invasiveness. Together, these changes inhibit PCa disease progression. Additionally, we identify a gene network involved in cell cycle regulation that is inhibited by AMPK activation. Strikingly, we show a correlation between this gene network and PGC1α gene expression in human PCa. Taken together, our findings support the use of AMPK activators for clinical treatment of PCa to improve patient outcome.

Keywords

AMPK; CP: Cancer; CP: Metabolism; PGC1α; cell cycle regulation; fatty acid oxidation; high-fat diet; lipogenesis; metabolism; metastasis; mitochondria; prostate cancer.

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