Scientists have explained the mysterious Warburg effect, which is observed in most cancer cells and consists in the fact that they produce energy differently than normal healthy cells. This phenomenon has been tried to understand 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 convert it into pyruvate during glycolysis, which, in turn, is oxidized in mitochondria, the energy-producing cell organelles. However, cancer cells use a more intense and faster form of glycolysis, fermenting glucose into lactic acid. This was thought to be due to defective mitochondria, but it was later found that these organelles functioned normally in cancer cells.
A team of researchers from the Sloan-Kettering Cancer Center in the U.S. discovered 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 proliferation, cell metabolism and avoidance of programmed cell death. When cells switch to Warburg metabolism, kinase activity increases, which in turn enables cells to divide rapidly.
The team studied immune cells, which also rely on an unusual form of metabolism. When an infection enters the body, the T cells engage the Warburg effect to divide rapidly. This switch is controlled by the enzyme lactate dehydrogenase A (LDHA), which is produced in response to signal transduction via the PI3K pathway. Interestingly, blocking LDHA negatively affects PI3 activity, which is due to the presence of a positive feedback loop between the kinase and ATP production. The loop allows immune cells to maintain a program to fight infection until it is eliminated.
According to the scientists, a similar mechanism is involved in cancer cells, which thus ensure their continued growth and division. The results of the study indicate that it is possible to fight tumors by blocking LDHA.