Fig. 8.

Roles for amplified oncogenes, EGFR, RNF139, and XIAP, to control pH via access to the systemic bicarbonate buffer system in aiding glioblastoma cells. Red cells and plasma in the blood stream (upper panels) remove carbons via CO₂ that is exhaled in the lungs. Transport of CO₂/HCO₃⁻ occurs in a relay fashion within the circulation. Large amounts of bicarbonate in the bloodstream buffer protons and levels are maintained via recycling in the kidneys where the protons carried by bicarbonate are expelled. Amplified EGFR and RNF139 may enhance expression of CA3 and CA12, respectively, to increase encoded tumor carbonic anhydrases (lower panel). In contrast, XIAP may reduce expression of CA12. Lactic acid membrane transporter, MCT4, is encoded by SLC16A3. The edge of a tumor cell is in the lowest panel. Red cells are depicted with reactions derived from other diagrams [78], [79], [80]. H⁺ ions (protons) from ATP breakdown during anaerobic metabolism involving lactic acid is a process explained elsewhere [81].