MIT Researchers Discover Why Cancer Cells Get Energy From Fermentation

Scientists have known for decades that cancer cells don't metabolize sugar in the same way normal cells do. Scientists have been trying since that discovery in the 1920s to figure out why cancer cells use a method for metabolizing sugar that is much less efficient. Scientists at MIT believe they have now found a potential answer to that question.

Researchers have shown that the metabolic pathway, known as fermentation, helps cells regenerate large quantities of a molecule called NAD+ needed to synthesize DNA and other essential molecules. The discovery accounts for why other types of cells that grow rapidly, such as immune cells, also switch to fermentation for their energy. Researcher Matthew Vander Heiden says that the team found under some circumstances, cells need to do more electron transfer reactions, which require NAD+ to make molecules like DNA.

Fermentation is a way cells can convert the energy found in sugar to ATP, which is a chemical cells use to store energy. Typically, mammalian cells break down sugar utilizing a process known as aerobic respiration to create much more ATP. Cells changeover to fermentation only if they don't have enough oxygen available to perform aerobic respiration.

In the 20s, the theory was that cancer sales used the more inefficient fermentation pathway because the mitochondria within the cancer cell may be damaged. However, the new MIT study finds this isn't the case. During the study, the MIT team suppressed the ability of the cancer cells to perform fermentation. They treated the cells with a drug that forces them to divert a molecule called pyruvate from the fermentation pathway into the aerobic respiration pathway.

It has been previously shown that blocking fermentation slows down the growth rate of cancer cells. The team then tried to restore the ability of the cell to proliferate while blocking fermentation. They attempted to stimulate the cells to produce NAD+, which helps cells dispose of extra electrons stripped out when molecules like DNA and proteins are produced. Researchers used a drug that stimulates NAD+ production, and the cells begin to proliferate again though they were unable to perform fermentation.

That led the team to theorize that NAD+ is needed more than ATP as the cells grow rapidly. The theory is switching to a less efficient method of producing ATP allows the cells to generate more NAD+ to help them grow faster.