Key mechanisms contributing to TME acidification include:
HIF-1α Activation: Hypoxia-inducible factor 1-alpha (HIF-1α) is often upregulated in tumors, promoting glycolysis and acid production. Carbonic Anhydrase IX (CAIX): This enzyme is overexpressed in many cancers and helps regulate intracellular pH by converting carbon dioxide to bicarbonate and protons. Proton Pumps: Increased expression of proton pumps such as V-ATPase helps export protons from cancer cells, acidifying the extracellular space.
