A new study from researchers at Washington University in St. Louis debunks the previous claim that cancer cells are intentionally wasting glucose, a common sugar found in food that is one of the most important nutrients in the body.
Genetic Engineering & Biotechnology News reported that cancer cells consume them at an astounding pace, which seems to make good sense because they have many syntheses. But they do not use the glucose very efficiently as they tend to release most of it as waste material.
Cancer Cells Metabolize Glucose Until They Can't
Mitochondria is the powerhouse of the cell that tightly controls what goes in and out of them. Famous biochemist Otto Warburg first discovered the wasteful nature of cancer cells back in the 1920s.
His discovery led to questions about why these cells do not harvest more energy from glucose, wherein Warburg postulates that mitochondria must be damaged in cancer cells.
However, more research revealed that it is not the case at all. Senior author Gary Patti, a member of Siteman Cancer Center at Barnes-Jewish Hospital and the School of Medicine, said that mitochondria are very much alive and functional in cancer cells. So, why do they metabolize so little that they consume in mitochondria?
According to Science Daily, Patti believes that this notion has been confounding, especially in the part where cancer cells prefer not to oxidize glucose in mitochondria. He noted that perhaps Warburg's legacy or because it happens extensively, assumptions of cancer cells being wasteful have continued.
Scientists have offered explanations as to why cancer cells might be wasteful of their glucose. Still, Patti and his team think these rationalizations may not be needed because cancer metabolism may not be as unusual as previously thought. The team believes cancer cells want to metabolize glucose in their mitochondria until they cannot.
He pointed out that almost all glucose makes its way to mitochondria when its amount is restricted by cancer cells. However, the speed of moving glucose-derived molecules into the cell's powerhouse cannot keep up as glucose consumption increases. Cancer cells only waste glucose when transport into the mitochondria is too slow.
Patti added that this is not radically a new metabolic paradigm as most cells oxidize glucose in mitochondria than excrete it. However, the findings suggest that cancer cells are no exception and seem to follow the same biochemical patterns as healthy cells.
Cells from cervical cancer
Metabolomics Helped Researchers in the Study
The discovery was made possible through the powerful technology called metabolomics. Patti noted that advances in the field of metabolomics and mass spectrometry have been extraordinary in the past decade and now it has been used to measure molecules in single cells.
In the study titled "Saturation of the Mitochondrial NADH Shuttles Drives Aerobic Glycolysis in Proliferating Cells," published in the journal Molecular Cell, metabolomics was combined with stable isotope trackers that enabled researchers to tag different parts of glucose so they could track it inside the cells where they could observe what enters the mitochondria and exits the cells.
The scientists found that the typical pathways for transporting fuel were getting saturated inside the cancer cells. The speed at which tumors consume glucose has been tracked by doctors to diagnose cancer and identify its stage, but it also led them to believe that limiting glucose intake or having a sugar-free diet could help kill cancer.
The findings of the new study question that strategy. Patti noted that such a method should be re-evaluated to think how best to target glucose metabolism in cancer.
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