In a new study published in Molecular Systems Biology, researchers from the University of California, Los Angeles, and their collaborators report that depriving cancer cells of glucose leads to cancer cell death, says a UCLA press release. Researchers focusing on cancer cells' increased consumption of glucose usually study the biochemical signals the cells use to regulate their altered metabolism, UCLA says. But in this study, Thomas Graeber and his colleagues investigated instead how the metabolism of glucose affects the biochemical signals in cancer cells. They found that glucose starvation leads to the activation of a metabolic and signaling amplification loop, which, in turn, causes the toxic accumulation of reactive oxygen species and eventual cancer cell death.
"To explain the seemingly contradictory result that glucose deprivation reduced viability and at the same time increased signaling, the authors used an unbiased systems-biology approach that included phospho-tyrosine mass spectrometry and other biochemical profiling techniques," UCLA says. "Assessing the 'crosstalk' between metabolism and signaling, they discovered that the glucose deprivation activates a positive feedback loop." Graeber adds that this study demonstrates what a fine balance between metabolism and signaling cancer cells need to survive. The team also showed in a cancer cell line that short-term glucose deprivation combined with tyrosine phosphatase inhibition leads to cell death — this, they add, could lead to new combination therapies for certain cancers.