The biology of cancer: metabolic reprogramming fuels cell growth and proliferation.
Cell proliferation requires nutrients, energy, and biosynthetic activity to duplicate all macromolecular components during each passage through the cell cycle. It is therefore not surprising that metabolic activities in proliferating cells are fundamentally different from those in nonproliferating cells. This review examines the idea that several core fluxes, including aerobic glycolysis, de novo lipid biosynthesis, and glutamine-dependent anaplerosis, form a stereotyped platform supporting proliferation of diverse cell types. We also consider regulation of these fluxes by cellular mediators of signal transduction and gene expression, including the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR system, hypoxia-inducible factor 1 (HIF-1), and Myc, during physiologic cell proliferation and tumorigenesis.
DeBerardinis
Ralph J
RJ
Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
Lum
Julian J
JJ
Hatzivassiliou
Georgia
G
Thompson
Craig B
CB
D000818:Animals; D049109:Cell Proliferation; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction
D051793:Hypoxia-Inducible Factor 1; D019869:Phosphatidylinositol 3-Kinases