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Glucose deprivation activates feedback loop that kills cancer cells, UCLA study shows
Date:6/26/2012

Compared to normal cells, cancer cells have a prodigious appetite for glucose, the result of a shift in cell metabolism known as aerobic glycolysis or the "Warburg effect." Researchers focusing on this effect as a possible target for cancer therapies have examined how biochemical signals present in cancer cells regulate the altered metabolic state.

Now, in a unique study, a UCLA research team led by Thomas Graeber, a professor of molecular and medical pharmacology, has investigated the reverse aspect: how the metabolism of glucose affects the biochemical signals present in cancer cells.

In research published June 26 in the journal Molecular Systems Biology, Graeber and his colleagues demonstrate that glucose starvation that is, depriving cancer cells of glucose activates a metabolic and signaling amplification loop that leads to cancer cell death as a result of the toxic accumulation of reactive oxygen species, the cell-damaging molecules and ions targeted by antioxidants like vitamin C.

The research, which involved UCLA scientists from the Crump Institute for Molecular Imaging, the Institute for Molecular Medicine, the California NanoSystems Institute, the Jonsson Comprehensive Cancer Center, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and the Department of Pathology and Laboratory Medicine, demonstrates the power of systems biology in uncovering relationships between metabolism and signaling at the network level.

"Most strikingly, our discovery that glucose withdrawal causes both cell death and increased tyrosine phosphorylation is intriguing because increased tyrosine kinase signaling is normally associated with cell growth," said Nicholas A. Graham, a senior postdoctoral scholar in Graeber's lab who helped design the project.

To explain the seemingly contradictory result that glucose deprivation reduced viability and at the same time increased signaling, the au
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Contact: Jennifer Marcus
jmarcus@cnsi.ucla.edu
310-267-4839
University of California - Los Angeles
Source:Eurekalert

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