The Role of Extra- and Intracellular pH Values in Regulation of the Tumor Process

The review presents and discusses data on the role of changes in pH outside and inside of a cell that are caused by aerobic glycolysis in tumor tissue. In comparison with normal tissue in a tumor, there is acidification of the intercellular space and an increase in pH inside the tumor cells. The main factor in the regulation of glycolysis is the HIF α transcription factor. The change in pH is due to the fact that the final product of glucose conversion is not pyruvate, but lactate. Lactate is transported across the cell membrane and acidifies the intercellular space. In addition, HIF α factor causes the transcription of a number of proton pumps and matrix proteinases, which are activated in the acidic environment of the intercellular space. The intercellular matrix is destroyed, which allows tumor cells to invade. The acidification of the intercellular space due to the functioning of proton pumps causes an increase in the pH inside the cells. An increase in intracellular pH stimulates the accelerated passage of cells through the phase G 2 cell cycle. The molecular mechanisms of this process are discussed. It is concluded that the main factors of the tumor process—invasion, accelerated proliferation, and genome instability are due to aerobic glycolysis (the Warburg effect).