PROS1 and neoplasm: Tumour cells can maintain pHi values by increasing expression and activation of pH-regulating proteins, some of which are HIF-1-dependent, such as the monocarboxylate transporter-4 (MCT-4), carbonic anhydrase IX (CAIX), sodium bicarbonate transporters, and sodium-proton exchangers, which release lactate, CO2/bicarbonate, and H+ from tumour cells.