A biologic mechanism in yeast cells may explain the relationship between sugar and malignant tumors, according to a recent study published in the journal Nature Communications. The nine-year research project may even influence personal medicine and diets for cancer patients. The study begins by looking closely at cancer cells’ appetite for sugar.
Scientists understand that cancer cells support their rapid reproduction by rewiring their metabolisms to take glucose, ferment it and produce lactate. Conversely, healthy cells continue with normal respiration, a process in which they take glucose and break it down into carbon dioxide and water.
This “switch of cancer cells from respiration to fermentation is something that was discovered by Otto Warburg, a German biochemist, about 70 or 80 years ago,” said microbiologist Johan M. Thevelein, senior author of the study and a professor at KU Leuven in Belgium. It is known as “the Warburg effect.”
Fermentation of sugar to lactic acid produces about 15 times less energy than respiration of sugar, Thevelein noted. Yet cancer cells “grow much more rapidly than normal cells, and yeast actually grows the fastest when they ferment,” he noted.
“This is weird,” he said, and it raises an important question: Is the Warburg effect a symptom of cancer — or a cause of it?
Searching for the answer, Thevelein and his colleagues experimented with yeast cells since, just like cancer cells, they are known to favor fermentation over respiration.
The researchers found an intermediate compound that is a “potent activator” of the RAS protein. RAS is a proto-oncogene: a gene that codes for proteins that help to regulate cell growth and differentiation. Proto-oncogenes can become oncogenes or cancer-causing genes when mutations occur. Mutant forms of RAS proteins are present in many tumors, Thevelein said. The new study, then, reveals “a vicious cycle,” he said.
As sugar is broken down in cells, the intermediate compound activates the RAS proteins, and this, in turn, stimulates cell proliferation, he said. This cycle seen in yeast cells might help explain the aggressiveness of cancer. “Very interesting,” said Dr. Jennifer Ligibel, chairwoman of the American Society of Clinical Oncology’s energy balance committee. Still, she urges caution in interpreting these findings.
“It’s important to not make too many jumps into a patient message based on a study of yeast,” she said.