The relationship between sugar and cancer has been made clearer by new research from Belgian scientists. The nine-year joint research project, undertaken by Vrije Universiteit Brussel, Katholieke Universiteit Leuven, and the Flanders Institute for Biotechnology, has led to a new understanding of how the Warburg effect, a phenomenon in which cancer cells rapidly break down sugars, stimulates tumour growth.

This breakthrough, which provides evidence for a positive correlation between sugar and cancer, could have far-reaching impacts on personalized diets for cancer patients.

The project, begin in 2008, focused mainly on the Warburg effect - the observation that tumours convert significantly higher amounts of sugar into lactate compared to healthy tissues. As one of the most prominent features of cancer cells, this phenomenon has been extensively studied and even used to detect brain tumours, among other applications.

But it has been unclear whether the effect is merely a symptom of cancer, or a cause.

Metabolic Deviation

Earlier research into cancer cell metabolism was chiefly on mapping out metabolic peculiarities. This new study elucidates the link between metabolic deviation and oncogenic potency in cancerous cells.

“Our research reveals how hyperactive sugar consumption of cancerous cells leads to a vicious cycle of continued stimulation of cancer development and growth. Thus, it is able to explain the correlation between the strength of the Warburg effect and tumour aggressiveness. This link between sugar and cancer has sweeping consequences. Our results provide a foundation for future research in this domain, which can now be performed with a much more precise and relevant focus,"

said co-leader Prof. Johan Thevelein, of Vrije Universiteit Brussel (VIB) and Katholieke Universiteit Leuven (KU Leuven).

Ras Proteins

One key to the breakthrough was yeast cell research, as these cells contain the same Ras proteins commonly found in tumour cells, which can cause cancer in mutated form. Using yeast as a model organism, the research team examined the connection between Ras activity and the highly active sugar metabolism in yeast.

“We observed in yeast that sugar degradation is linked via the intermediate fructose 1,6-bisphosphate to the activation of Ras proteins, which stimulate the multiplication of both yeast and cancer cells. It is striking that this mechanism has been conserved throughout the long evolution of yeast cell to human. The main advantage of using yeast was that our research was not affected by the additional regulatory mechanisms of mammalian cells, which conceal crucial underlying processes.

We were thus able to target this process in yeast cells and confirm its presence in mammalian cells. However, the findings are not sufficient to identify the primary cause of the Warburg effect. Further research is needed to find out whether this primary cause is also conserved in yeast cells."

explained Prof. Thevelein.

Although the finding is significant, it does not follow that eating a low-sugar diet could change a cancer diagnosis.

“The findings are not sufficient to identify the primary cause of the Warburg effect. Further research is needed to find out whether this primary cause is also conserved in yeast cells,"

said Prof. Thevelein.

The research was supported fellowships from the Agency for Innovation by Science and Technology and the Research Fund of the KU Leuven to H.Q., and by grants from the Fund for Scientific Research—Flanders, Interuniversity Attraction Poles Network P6/14 and P7/40, the Research Fund of the KU Leuven, and the Belgian Foundation Against Cancer

Ken Peeters, Frederik Van Leemputte, Baptiste Fischer, Beatriz M. Bonini, Hector Quezada, Maksym Tsytlonok, Dorien Haesen, Ward Vanthienen, Nuno Bernardes, Carmen Bravo Gonzalez-Blas, Veerle Janssens, Peter Tompa, Wim Versées & Johan M. Thevelein Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras Nature Communications 8, Article number: 922 (2017) doi:10.1038/s41467-017-01019-z

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