Abstract: Series 104, Lecture 6
The Harvey Lectures Series 104 (2008—2009)
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Lecture #6: Thursday, April 16, 2009 — Time and Location
Fueling Cancer Cell Growth
Craig B Thompson, MD
Professor of Medicine
Director, Abramson Cancer Center
University of Pennsylvania
Philadelphia, Pennsylvania
In nontransformed cells the uptake of nutrients is directly determined by growth factor signaling. In the absence of growth factor receptor engagement, mammalian cells must depend on autophagy to supply bioenergetic substrates to maintain ATP production and survival. In contrast, when lineage-specific survival receptors are maximally stimulated, they can direct the cell to take up glucose in excess of its needs, resulting in the conversion of intermediate metabolism to a form of aerobic glycolysis. This diverts available amino acids into protein synthesis and establishes an alternative mitochondrial/cytoplasmic citric acid cycle that converts glucose into lipids, defining a form of intermediate metabolism that is adaptive for the support of cell growth. However, the conversion from growth to proliferation depends on a cell's ability to switch from glycolysis to glutaminolysis. This conversion allows glucose metabolites to be redirected into nucleotide biosynthesis, with glutamine replacing glucose as the cellular source of NADPH and lipid biosynthesis. Evidence that these steps of metabolic reprogramming for cell growth/proliferation are under the direct control of oncogenic signaling in cancer cells will be presented.