AMP-activated protein kinase regulates cancer cell growth and metabolism via nuclear and mitochondria events

J Cell Mol Med. 2019 Jun;23(6):3951-3961. doi: 10.1111/jcmm.14279. Epub 2019 Apr 16.


Adenine monophosphate-activated protein kinase (AMPK) is a fuel sensing enzyme that is activated in shortage of energy and inhibited in its surplus. Cancer is a metabolic disease characteristic of aerobic glycolysis, namely Warburg effect, and possesses heterogeneity featured by spatiotemporal hypoxia and normoxia, where AMPK is deeply implicated. The present study delineates the regulation of mitochondrial functions by AMPK in cancer cells. On the one hand, AMPKα subunit binds to mitochondria independently of β subunit and targeting AMPK to mitochondria facilitates oxidative phosphorylation and fatty acid oxidation, and inhibits glycolysis. As such, mitochondrial AMPK inhibits the growth of cancer cells and tumorigenesis. On the other hand, ablation of the β subunits completely abolishes AMPK activity and simultaneously leads to decreases in mitochondria DNA and protein contents. The effect of the β deletion is rescued by overexpression of the active mutant of bulky AMPKα1 subunit. In conjunction, the transcriptional factors PGC1α and Nrf-1 are up-regulated by LKB1/AMPK, an event that is abolished in the absence of the β subunits. Intriguingly, the stimulation of mitochondria biogenesis is not achieved by mitochondria-targeted AMPK. Therefore, our study suggests that AMPK inhibits cancer cell growth and tumorigenesis via regulation of mitochondria-mediated metabolism.

Keywords: AMP-activated protein kinase; Warburg effect; cancer growth; glycolysis; mitochondrial function; oxidative phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism*
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Glycolysis / genetics
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Nude
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Oxidation-Reduction
  • Oxidative Phosphorylation
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Rats
  • Transplantation, Heterologous
  • Transplantation, Homologous


  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • AMP-Activated Protein Kinases