Scientists have explained the mysterious Warburg effect that is observed in most cancer cells, which is that they produce energy differently from normal healthy cells. They tried to understand this phenomenon for a hundred years, but none of the hypotheses has yet been recognized as valid. A possible solution to the age-old mystery has been published in the leading scientific journal Science.
To obtain energy in the form of ATP molecules, cells consume glucose and, during glycolysis, process it into pyruvate, which, in turn, is oxidized in mitochondria – energy-producing cell organelles. However, cancer cells use a more intense and faster form of glycolysis, fermenting glucose into lactic acid. It was assumed that this is due to defective mitochondria, but later it turned out that these organelles in cancer cells function normally.
A group of researchers from the Sloan-Kettering Cancer Center in the United States have found a link between the Warburg effect and the enzyme kinase PI3 (phosphoinositide 3-kinase). This molecule plays a key role in the so-called PI3K / AKT / mTOR signaling pathway, which regulates cell growth and reproduction, their metabolism, and avoidance of programmed cell death. When cells switch to Warburg metabolism, kinase activity increases, which in turn allows cells to divide rapidly.
The team examined immune cells that also rely on an unusual form of metabolism. When an infection enters the body, T cells use the Warburg effect to divide rapidly. This switch is controlled by the enzyme lactate dehydrogenase A (LDHA), which is produced in response to signaling through the PI3K pathway. Interestingly, blocking LDHA negatively affects PI3 activity due to the presence of a positive feedback loop between kinase and ATP production. The loop allows immune cells to maintain an infection-fighting program until it is eliminated.
According to scientists, a similar mechanism is at work in cancer cells, which thus ensure continuous growth and division. The results of the study indicate the possibility of fighting tumors through blocking LDHA.