Scientists have clarified how the Warburg effect, a phenomenon in which cancer cells rapidly break down sugars, stimulates tumor growth.
The discovery, which has been outlined in the journal Nature Communications, provides evidence for a positive correlation between sugar and cancer, which the researchers say could have implications for tailor-made diets for cancer patients.
The nine-year joint research project by the University of Leuven was started in 2008. Its main focus was the Warburg effect, or the observation that tumors 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 tumors, among other applications. Until now it has been unclear whether the effect is merely a symptom of cancer, or a cause.
Earlier research into cancer cell metabolism focused on mapping out metabolic peculiarities, but this study clarifies the link between metabolic deviation and oncogenic potency in cancerous cells.
Johan Thevelein, the study’s lead author, said: ‘Our research reveals how the 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 tumor 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.’
Using yeast as a model organism (yeast cells contain the same ‘Ras’ proteins commonly found in tumour cells, which can cause cancer in mutated form) the research team examined the connection between Ras activity and the active sugar metabolism in yeast.
Thevelein said: ‘We observed in yeast that sugar degradation is linked via the intermediate fructose 1,6-biophosphate 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.’