Figure 1.

An increase in aerobic glycolysis to lactate in the tumor cells leads to an accumulation of protons that are actively removed from the cell by proton pumps (in light orange) and transporters (green). This activity produces an accumulation of protons in the extracellular media and a concomitant pH increase at the cytosol. The augmented glycolytic flux is driven by the action of several oncogenes (in bold red letters), that induce the expression and activation of most of the glycolytic enzymes. For a comprehensive review on the role of oncogenic signals in the control of glycolysis see reference 9. HK2: hexokinase 2; PFK1: phosphofructokinase 1; LDHA: lactate dehydrogenase A; GLUT1: glucose transporter 1; pH_i: intracellular pH; pHe: extracellular pH.