VIB/KU Leuven
VIB and University of Leuven - How Sugar May Stimulate Cancer
It has been known for a long time that there is a close correlation between the overactive sugar breakdown in cancer cells (the so-called Warburg effect) and the aggressiveness of a cancer. However, whether the overactive sugar breakdown is merely a symptom of the cancer or whether it may play a role in stimulating the cancer has remained unclear. Our work has now revealed for the first time a direct molecular connection between sugar breakdown and activation of cancer.
We discovered that a major intermediate compound in the sugar breakdown pathway, fructose-1,6-bisphosphate, is a potent activator of the Ras proteins. They are present in mutated overactive form in many cancer types and the mutant RAS genes are among the best known oncogenes. We discovered this mechanism first in yeast cells and then showed that it is conserved in mammalian cells. Interestingly, yeast cells and cancer cells share a preference for sugar breakdown by fermentation rather than by respiration, even under aerobic conditions, which is exceptional.
This remarkable conservation in evolution underscores the likely importance of this new mechanism in cellular regulation. Since it is well known that RAS and other oncogenes stimulate sugar breakdown, causing increased fructose-1,6-bisphosphate levels, the new mechanism appears to create a vicious cycle by which sugar breakdown stimulates Ras and Ras stimulates sugar breakdown, explaining the close correlation between the rate of overactive sugar breakdown and the aggressiveness of cancer. The new mechanism tends to provide support for the data in the scientific literature that connect a better outcome of cancer chemotherapy with sugar-poor diets.