By Meenu Johnkutty ’21

Researchers from the Laboratory of Molecular Cell Biology in Belgium have achieved a breakthrough in cancer research. Their project, which began in 2008, finally came to completion after nine long years. The scientists’ focus was the Warburg effect, a phenomenon in which cancer cells rapidly break down sugar molecules, stimulating tumor growth. This effect was named after Nobel laureate Otto Heinrich Warburg, who linked tumor production to the “replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.” Though a number of researchers had previously conducted extensive studies of the Warburg effect, none had been able to determine whether the rapid breakdown of sugar molecules is a cause or a symptom of cancer.

To further the study of the Warburg effect, Belgian researchers chose yeast as their model organism. Because yeast contains “Ras molecules,” proteins that are commonly expressed in tumor cells, this decision proved to be incredibly advantageous to the study. Moreover, regulatory mechanisms, which would otherwise be found in mammalian cells, are absent in yeast, therefore; scientists were able to focus specifically on isolated relationships within the yeast’s metabolic pathway without obstruction.

To detect and visualize metabolic pathways within the yeast, the scientists performed multiple rounds of cell assays, fluorescence assays, western blotting, and other cell isolation techniques. Results revealed that the intermediate between sugar degradation and Ras production is fructose 1,6-bisphosphate. Next, to isolate the relationship between Ras molecules and the fructose 1,6-bisphosphate, the scientists deleted the genes responsible for encoding phosphofructokinase 1, the product formed right before fructose 1,6-bisphosphate in the glucose metabolism chain. As a result, cells which lacked both regulatory genes for phosphofructokinase 1 created no Ras, while cells which had one of these genes deleted generated little Ras. The deletion of these genes allowed scientists to pinpoint the role of fructose 1,6-bisphosphate in producing Ras molecules.

This research has numerous implications for cancer treatment: knowing that sugar has a direct link with Ras allows dieticians and physicians to tailor diets specifically for cancer patients. Moreover, this study has paved the way for scientists to perform further precise and defined research on the relationship between sugar and cancer and thereby achieve additional breakthroughs.

References:

1. K. Peters, et. al., Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras. Nature Communications 8, (2017). doi: 10.1038/s41467-017-01019-z.
2. Image retrieved from: https://www.nature.com/articles/s41467-017-01019-z#Sec2