Insulin, growth factors, and cancer cell energy metabolism: an hypothesis on oncogene action.
The hexokinase-mitochondrial acceptor theory provides a model of insulin action which unifies the metabolic effects of this hormone and suggests that these result from insulin's stimulatory effect on mitochondrial ATP synthesis. There are similarities between these changes in cells exposed to insulin and in mitochondria of transformed cell lines and cancer cells, where an increased binding of hexokinase to mitochondria is observed. This phenomenon may play a key role in the high rates of glycolysis sustained by cancer cells under aerobic conditions. Structural and functional evidence support the hypothesis that certain growth factors and oncogenes act through stimulation of oxidative phosphorylation via promoting HK binding to mitochondria.
Golshani
S
S
University of Southern California School of Medicine, Los Angeles 90030.
D000818:Animals; D004734:Energy Metabolism; D006133:Growth Substances / Q000502:physiology*; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009857:Oncogenes
D006133:Growth Substances; D007328:Insulin; D006593:Hexokinase