Massachusetts Institute of Technology research sheds light on the long-lasting question of why cancer cells are getting their energy from fermentation. During the 1920s, Otto Warburg, a chemist, discovered that cancer cells do not metabolize sugar in the same manner that healthy cells typically do.
From that time, scientists have attempted to find out why cancer cells are using this substitute pathway, which is much less effective.
As mentioned, biologists at MIT now discovered a possible answer to this long-lasting question. In research published in Molecular Cell, the researchers presented that this metabolic pathway identified as fermentation helps cells redevelop large numbers of a molecule identified as NAD+, which they should synthesize DNA and other essential molecules.
According to SciTechDaily, the MIT biologists' study results also account for the reason other types of speedily proliferating cells like immune cells, "switch over fermentation."
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The MIT biologists’ study results also account for the reason other types of speedily proliferating cells like immune cells, ‘switch over fermentation.’
A Century-Old Paradox
MIT's associate professor of biology, Matthew Vander Heiden, an associate director of MIT's Koch Institute for Integrative Cancer Research, said, this has really been a century-old "paradox that many people have tried" explaining in various ways.
The researchers found that, under certain conditions, cells should do more of the electron transfer reactions, which need NAD+, to make molecules like DNA.
Vander Heiden is the new study's lead author, and the lead authors are graduate and postdoc of MIT Alba Luengo, Ph.D. '18, and Zhaoqi Li, also a graduate student.
'Fermentation'
Fermentation is one way for cells to convert the energy that exists in sugar to ATP, a chemical used by cells for energy storage for all their needs.
Nevertheless, mammalian cells typically break down the sugar by using a process known as "aerobic respiration," yielding much more ATP.
Cells usually shift over to fermentation only when they do not have adequate oxygen available to carry out aerobic respiration.
Since the discovery of Warburg, scientists have put forth several theories for a reason cancer cells are switching to the inefficient fermentation pathway.
Originally, Warburg suggested that the mitochondria of cancer cells, where aerobic respiration takes place, might be impaired, although this the said report specified, "turned out to be the case.
Attempt to Solve the Paradox
The biologists tested this notion in other types of swiftly multiplying cells, including immune cells. They found that blocking fermentation but enabling substitute approaches of NAD+ production allowed cells to continue dividing rapidly.
The researchers observed a similar phenomenon in non-mammalian cells like yeast, which performs on a different fermentation type that generates ethanol.
Heiden said, not all proliferating cells need to do this. It is really just cells that grow very rapidly. If sales are growing quite fast that their demand to produce stuff outstrips the amount of ATP they are burning, that is when they flip over into this metabolism type. Therefore, it's solving, "in my mind, many of the paradoxes that have existed," added Heiden.
The study results propose that drugs forcing cancer cells to go back to aerobic respiration rather than fermentation could provide a possible way of treating tumors. Drugs that prevent NAD+ production could have an advantageous impact, too, explained the biologists.
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